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112 publications mentioning rno-mir-29a (showing top 100)

Open access articles that are associated with the species Rattus norvegicus and mention the gene name mir-29a. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 280
The arrest of NSE and Tau expression induced by miR-29a inhibition was partially blocked by REST knockdown, indicating that miR-29a regulated the expression of NSE and Tau through targeting REST gene. [score:11]
The present study has demonstrated that the expression of REST decreases upon neuronal differentiation of MSCs, which is partially due to miR-29a upregulation, and miR-29a promotes neuronal differentiation of MSCs through targeting REST, which provides advances in neuronal differentiation research and stem cell therapy for neurodegenerative diseases. [score:10]
During the neuronal differentiation of MSCs, miR-29a inhibition blocked the downregulation of REST, as well as the upregulation of SNAP25, L1CAM, NSE and Tau. [score:9]
Among the 14 miRNA upregulated in MSC-NCs, rno-miR-29a and rno-miR-29b were predicted to target REST analyzed by TargetScan (http://www. [score:8]
REST was downregulated, and SNAP25 and L1CAMby were upregulated by miR-29a knockin. [score:8]
Meanwhile, miR-29a knockin significantly decreased the expression of REST and increased the expression of SNAP25 and L1CMA in MSCs, but did not significantly affect the expression of NSE and Tau. [score:8]
However, the present study showed that downregulation of REST by miR-29a overexpression did not increased the expression of NSE and Tau. [score:8]
We found that forced expression of miR-29a decreased REST expression in MSCs through directly targeting REST, indicating the potential role of miR-29a to modulate the neurogenesis of MSCs. [score:8]
The forced expression of miR-29a decreased the expression of REST and increased the expression of SNAP25 and L1CAM (Fig. 4E). [score:7]
NSE and Tau genes were upregulated by REST knockdown in MSC-NCs with miR-29a inhibition. [score:7]
Among 14 upregulated miRNAs, miR-29a was validated to target REST gene. [score:6]
In MSC-NCs with miR-29a inhibition, REST knockdown increased the expression of NSE and Tau (Fig. 4D). [score:6]
miR-29a knockdown increased the expression of REST and decreased the expression of SNAP25, L1CAM, NSE and Tau in MSC-NCs (Fig. 4C). [score:6]
REST knockdown rescued the effect of miR-29a inhibition on the expression of NSE and Tau. [score:6]
miR-29a regulates neurogenic markers through targeting REST in mesenchymal stem cells, which provides advances in neuronal differentiation research and stem cell therapy for neurodegenerative diseases. [score:6]
miR-29a affects the expression of NSE and Tau through directly targeting REST. [score:6]
REST gene was upregulated by miR-29a inhibition. [score:6]
Therefore, we detected the expression of alkaline phosphatase (ALP), a marker of osteogenesis [43], and found that miR-29a knockin did not increase the expression of alkaline phosphatase (ALP) in MSC (Figure S2). [score:6]
Meanwhile, SNAP25, L1CAM, NSE and Tau genes were downregulated by miR-29a inhibition. [score:6]
We supposed that the miR-29a might regulate the expression of NSE and Tau through targeting REST gene during the neuronal differentiation of MSCs. [score:6]
The present study showed that miR-29a, also a tumor suppressor [45], may be a safer choice to arrest REST expression and balance the tumor formation in cell therap. [score:5]
miR-29a expression was significantly decreased after lentiviral infection of miR-29a inhibitor (Fig. 4A). [score:5]
We detected the expression of NSE and Tau, both are neuronal specific markers, and found it was not significantly increased by miR-29a over -expression. [score:5]
0097684.g004 Figure 4(A) Lentiviral infection of miR-29a inhibitor decreases miR-29a expression in MSCs. [score:5]
However, single miR-29a knockin did not significantly upregulate NSE or Tau gene (Fig. 4E). [score:5]
It is noteworthy that the exogenic expression of miR-29a did not effectively initiate the neuronal differentiation of MSCs, although it decreased the expression of REST gene. [score:5]
Considering that miR-29a and miR-29b have overlapped predicted target genes and the expression change of miR-29a is more outstanding, we chose miR-29a for further studies. [score:5]
REST is a direct target of miR-29a. [score:4]
The knockdown of REST was conducted to show that miR-29a affected this process through targeting REST. [score:4]
The expression of NSE and Tau was not significantly changed by miR-29a knockin. [score:4]
We are the first one to report the upregulation of miR-29a/b in MSC-NCs. [score:4]
We then showed that the downregulation of REST is modulated by miR-29a. [score:4]
Previous studies have detected the expression change of miR-29s during the neuronal development [38], [39], whereas, we are the first one to go deeply and discuss the role of miR-29a. [score:4]
miR-29a/b-1 express in primary cultures of neuronal and glial cells [39]. [score:3]
It is remarkable that miR-29a mainly affects the expression of neuronal markers, but not the cell shape in MSCs after neuronal induction (Figure S1). [score:3]
The present results indicate that the differentiation process is complicated, and mere miR-29a expression cannot completely trigger it. [score:3]
Then we demonstrated that miR-29a modulates neuronal differentiation through targeting REST in MSCs. [score:3]
luc-UTR vectors was constructed by cloning predicted miR-29a target region or its mutant control into the NheI and SalI sites of the pmirGLO luciferase vector (Promega, Madison, WI) using the PCR generated fragments. [score:3]
miR-29a modulates neuronal differentiation of MSCs through targeting REST. [score:3]
0097684.g003 Figure 3. (A) miR-29a and miR-29b are predicted to target REST upon the neuronal differentiation of MSCs. [score:3]
MSCs were transfected with miR-29a inhibitor for 4 d, then 1×10 [6] MSCs were plated, and 20 µl of virus suspension (at an MOI of 50) was added. [score:3]
miR-29a modulates neuronal differentiation of MSCs by targeting REST. [score:3]
After lentiviral infection of miR-29a precursor or scramble, MSCs expressed EGFP protein. [score:3]
Figure S1 Forced expression of miR-29a in MSCs. [score:3]
Figure S2 qRT-PCR results of ALP mRNA expression in MSCs transfected with miR-29a precursor. [score:3]
The lentivirus containing miR-29a inhibitor and its control was obtained from Baoke Bio-Technology Co. [score:3]
The expression of ALP mRNA in MSCs transfected with miR-29a precursor is not different from that in MSCs transfected with scramble. [score:3]
Therefore, we used the lentivirus containing siRNA against REST to co-infect MSCs with miR-29a inhibitor. [score:3]
MSCs were infected with lentivirus containing miR-29a inhibitor or control. [score:3]
The vectors, including REST-wt, REST-mut and control, were transfected into miR-29a lentivirus-infected 293 cells in which miR-29a was overexpressed, respectively. [score:3]
We further showed that miR-29a modulates neuronal differentiation through targeting REST in MSCs. [score:3]
Among those differently expressed microRNAs, miR-291a-5p, mir-294, miR-29a, and miR-29b were further detected by qRT-PCR, and the results were consistent with the microRNA array analysis (Fig. 2C). [score:3]
After analyzing miRNAs profiles in MSCs and MSC-NCs, we found that the expression of miR-29a increases during this process. [score:3]
MSCs with miR-29a knockdown presents neuron shape after induction. [score:2]
miR-29a knockin did not significantly change cell morphology. [score:2]
In order to study the role of miR-29a upon the neurogenesis of MSCs, we first conducted loss of function experiment. [score:1]
The human miR-29 family of microRNAs has three mature members, miR-29a, miR-29b, and miR-29c. [score:1]
However, it is still possible that miR-29a affects the cell morphology of MSCs upon neuronal differentiation using other means. [score:1]
The lentiviral vectors containing miR-29a precursor (RmiR6139-MR03), scramble control (CmiR0001-MR03) were obtained from GeneCopoeia Inc. [score:1]
Gain and loss of function experiments were used to study the role of miR-29a upon neuronal differentiation of MSCs. [score:1]
Genetic manipulation with miR-29a gain-of-function is prospective to promote the production of neurons from MSCs. [score:1]
MSCs maintained the normal cell morphology after lentiviral infection of miR-29a precursor. [score:1]
Kapinas et al [41], [42] have shown that miR-29a promotes osteoblast differentiation. [score:1]
The alignment of the seed regions of miR-29a with REST 3′ UTR are shown. [score:1]
The present study demonstrated that miR-29a modulates the neuronal differentiation of MSCs. [score:1]
We also conducted gain of function experiment by lentiviral transfection of miR-29a precursor in MSCs. [score:1]
The cells were cultured in 5% CO [2] at 37°C for 2 d. 293 cells were infected with lentivirus carrying miR-29a precursor for 2 d. Then the cells were transfected with pmirGLO-REST-wt, pmirGLO-REST-mut or pmirGLO-ctrl using Lipofectamine 2000 (Invitrogen). [score:1]
The REST 3′-UTR containing the miR-29a binding site and its mutant were cloned into the pmirGLO vector downstream of the luciferase ORF, respectively. [score:1]
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[+] score: 275
Conversely, inhibition of mTORC1 signaling resulted in up-regulation of miR-29 expression and suppressed MCL-1 expression in cardiomyocytes. [score:12]
Moreover, since DM is associated with either insulin deficiency or a lack of insulin signaling, we also posited that insulin would suppress the expression of the miR-29 family in cardiomyocytes and up-regulate MCL-1 expression. [score:10]
Data presented here shows that insulin down-regulates the expression of diabetic marker miR-29 family miRNAs in mouse cardiomyocytes and preserves the expression of cardioprotective MCL-1. Consistent with this insulin effect, 11-week old hyperinsulinemic ZDF rats only had a mild loss of MCL-1 expression and did not show any damage in myocardium. [score:10]
Conversely, inhibition of mTORC1 signaling by Rap or inhibitors of mTORC1 substrates significantly increased expression of miR-29 family miRNAs and suppressed cardioprotective MCL-1 in mouse cardiomyocytes. [score:9]
Since MCL-1 is a target of miR-29 family miRNAs, and Rap treatment increases miR-29 expression, we investigated whether a miR-29 inhibitor cocktail (inhibitors of miR-29a, b and c) would improve MCL-1 expression in Rap treated HL-1 cells. [score:9]
Since miR-29 suppresses MCL-1 and the miR-29 family miRNAs are elevated in DM we hypothesized that one of the mechanisms by which DM promotes heart disease is by causing dysregulation of the miR-29-MCL-1 axis and suppressing MCL-1 levels in cardiomyocytes that can lead to cardiomyocyte disorganization. [score:8]
B) Expression of miR-29 family miRNAs (miR-29a, b and c) in mouse cardiomyocyte HL-1 cells is suppressed by treatment with INS (100 nM; 12 h) and up-regulated by treatment with Rap (10 nM; 12 h). [score:8]
Transfection of HL-1 cells with miR-29 inhibitor cocktail reversed Rap -mediated suppression of MCL-1 expression. [score:7]
analysis using anti-MCL-1 antibody showed that Rap treatment substantially suppressed MCL-1 expression in HL-1 cells transfected with Allstars negative control siRNA, but not in HL-1 cells transfected with miR-29 inhibitor cocktail (Fig. 2D). [score:7]
We have shown in vitro that a miR-29 inhibitor cocktail could reverse Rap -mediated suppression of MCL-1 protein expression in cardiomyocytes. [score:7]
In non-obese diabetic (NOD) mice, up-regulation of miR-29a, b and c caused pancreatic β-cell death via suppression of the myeloid cell leukemia 1 (MCL-1) gene, an essential member of the pro-survival BCL-2 family genes, and marked the first stage of type 1 DM (T1DM) [15]. [score:6]
Since increased expression of different members of miR-29 family is associated with DM, we tested the effects of insulin that attenuates the progression of DM, and rapamycin (Rap) that promotes the progression of DM, on the expression of miR-29 family miRNAs in HL-1 cells. [score:5]
We undertook this study to uncover the role of microRNA miR-29 family and its target MCL-1, a pro-survival molecule that is critical for cardiomyocyte survival under stress, in the myocardium damage seen in diabetic heart disease. [score:5]
However, suppression of hyperinsulinemia by Rap in the absence of regulation of hyperglycemia as seen in Rap -treated ZDF rat promotes severe dysregulation of cardiac miR-29-MCL-1 axis that leads to disruption and loss of myofibril bundle organization. [score:5]
This would have led to the up-regulation of all miR-29 family miRNAs in their heart tissues that resulted in the severely dysregulated miR-29-MCL-1 axis in Rap -treated ZDF rats. [score:5]
Since Rap-treatment increased miR-29 levels and suppressed MCL-1 mRNA levels in mouse HL-1 cardiomyocytes, we tested whether Rap-treatment would increase cardiac miR-29 family miRNAs and suppress cardiac MCL-1 mRNA even further in young ZDF rats. [score:5]
Further studies are needed to also confirm that in in vivo rodent mo dels a miR-29 inhibitor cocktail would improve cardiac MCL-1 protein expression. [score:5]
Insulin treatment strongly suppressed miR-29a, b and c in cardiomyocytes whereas Rap treatment significantly enhanced expression levels of all three miR-29 family members in HL-1 cardiomyocytes (Fig. 1B). [score:5]
D) staining with anti-MCL-1 antibody and nuclear stain DAPI in HL-1 cells transfected with either (a) Allstars negative siRNA and (b) Allstars negative siRNA and treated with Rap (10 nM), or (c) miR-29 inhibitor cocktail (mirVana miRNA inhibitors for miR-29a, b and c) and treated with Rap (10 nM). [score:5]
20 nM of miR-29 inhibitor cocktail (mirVana miRNA inhibitors for miR-29a, b and c) or 20 nM Allstars negative siRNA (Qiagen) was used for transfection. [score:5]
Though rapamycin has well-established cardioprotective effects, an additional increase in miR-29 family miRNAs due to mTORC1 inhibition in the heart tissues of DM patients can potentially suppress MCL-1 and exacerbate cardiomyocyte disorganization and cardiac damage. [score:5]
Since insulin suppressed miR-29 in HL-1 cardiomyocytes, we posited that insulin would improve expression of MCL-1 in these cells. [score:5]
In brief, the suppression of miR-29 expression by insulin could be a previously unidentified cardioprotective mechanism in hyperglycemia. [score:5]
Regulation of miR-29 target MCL-1 by insulin and rapamycin in mouse cardiomyocytes. [score:4]
This observation implied that miR-29 family miRNAs regulate MCL-1expression in HL-1 cardiomyocytes. [score:4]
Though 11-week old ZDF rats had a mild dysregulation of miR-29-MCL-1 axis that resulted in about 45% suppression of MCL-1, no visible differences were observed in the histopathology of the RV tissues between ZL and ZDF rats. [score:4]
These data suggested that a miR-29-MCL-1 axis, similar to that seen in mouse and human pancreatic β-cells [15] exists in mouse cardiomyocytes and it is regulated by insulin and rapamycin, an mTORC1 inhibitor. [score:4]
We only observed a mild dysregulation of miR-29–MCL-1 axis at this stage and a 45% suppression of MCL-1 mRNA (Figs. 3I and 3J). [score:4]
miR-29a was identified as one of the miRs that was up-regulated in the serum of children with Type 1 DM (T1DM) [8]. [score:4]
Therefore, dysregulation of miR-29-MCL-1 axis caused by loss of insulin and mTORC1 inhibition is a major factor in promoting myocardial damage in DM in ZDF rats. [score:4]
Collectively, our data shows the steps in the dysregulation of miR-29-MCL-1 axis in heart tissues during the progression of DM as shown in Fig. 6. Briefly, at the age of 11 weeks, healthy ZL rats show basal level expression of miR-29 and MCL-1 and their myocardium is well organized. [score:4]
Expression of miR-29a and b were significantly higher in the myocardium of ZDF rat, but miR-29c was not significantly different between ZL and ZDF myocardium. [score:3]
miR-29 family miRNA expression pattern. [score:3]
RAP for miR-29 a, b, and c. The role of the miR-29-MCL-1 axis in the progression of DM -associated heart disease is not known. [score:3]
Quantitative trait loci (QTLs) associated with rat miR-29a and b highlight potential involvement of miR-29a and b in cardiovascular diseases (Fig. 1A). [score:3]
Since we observed that insulin could suppress miR-29 family miRNAs in cardiomyocyte HL-1 cells, it is conceivable that the lack of significant increase in miR-29c in the myocardium of 11-week old ZDF rats despite severe hyperglycemia could be due to their compensatory hyperinsulinemia (a 14-fold increase in plasma insulin). [score:3]
Expression of all three miR-29 family miRNAs (a, b and c) were significantly higher (at least 2 fold for each miRNA) in ZDF myocardium. [score:3]
A) The miR-29a/b cluster is associated with cardiovascular diseases. [score:3]
Though insulin treatment could induce phosphorylation of S6K1 rapidly, in this study we chose a 12 hr treatment to be consistent with the treatment time used for determining the changes in miR-29 and an MCL-1 mRNA expression in response to insulin in HL-1 cells. [score:3]
Cardiac tissues of 15-week old Rap treated ZDF-rats (Rap treatment from 9-weeks to 15-weeks) displayed a ∼2-fold increase in miR-29 family miRNAs and a 4-fold suppression of MCL-1 mRNA. [score:3]
Since insulin is an activator of the nutrient sensor kinase mammalian target of rapamycin complex 1 (mTORC1), we further posited that mTORC1-signaling mediates insulin's effects on miR-29-MCL-1 axis. [score:3]
However, qRT-PCR showed that Rap treated ZDF rats had at least a 2-fold increase in the expression of all miR-29 family members (miR-29a, b and c) (Fig. 4E). [score:3]
This observation may have important clinical relevance given the fact that patients with DM are reported to have an increase in miR-29 expression [8], [44]. [score:3]
Increased expression of diabetic marker miR-29 family miRNAs is seen in rodent mo dels of DM and in young and adult diabetic patients with T1DM or T2DM. [score:3]
0103284.g001 Figure 1A) The miR-29a/b cluster is associated with cardiovascular diseases. [score:3]
Therefore, we conclude that regulation of miR-29-MCL-1 axis by insulin is a cardioprotective mechanism and compensatory hyperinsulinemia in conditions of hyperglycemia would regulate miR-29-MCL-1 axis in diabetic heart and prevent significant myocardial damage in young (11- and 15-week) ZDF rats. [score:3]
Suppression of miR-29 by anti-miR-29 oligomers protects against myocardial ischemia-reperfusion injury, abdominal aortic aneurism and diabetic nephropathy [9]– [13]. [score:3]
HL-1 cells were transfected with either Allstars negative control siRNA or miR-29 inhibitor cocktail and after 8 hours of transfection subjected to treatment with Rap (10 nM) overnight. [score:3]
Progressive dysregulation of cardiac miR-29-MCL-1 axis in DM and its correlation with cardiac damage. [score:2]
Based on the data presented here, we contend that the normal functioning of miR-29-MCL-1 axis is an important cardioprotective mechanism regulated by insulin that exists in female mouse atrial cardiomyocytes and male ZDF rat heart tissue. [score:2]
In contrast Rap -treated ZDF rats have very low INS, severe hyperglycemia, and severe dysregulation of miR-29-MCL-1 axis. [score:2]
These data suggest that cardiac miR-29-MCL-1 axis is mildly dysregulated in 11-week old ZDF rats that suffer from DM. [score:2]
I: qRT-PCR analysis data showing the comparative expression levels of miR-29 family miRNAs in myocardium of ZDF rats compared to that in the myocardium of ZL rats. [score:2]
To our knowledge this is the first report that shows insulin is a regulator of miR-29 family miRNAs. [score:2]
For this study, we focused on the RV of ZDF rat heart since RV dysfunction from structural and functional perspectives has been described previously in young ZDF rats [5], [6] and therefore the baseline parameters were easy to compare in the context of regulation of the miR-29-MCL-1 axis. [score:2]
Our in vitro studies on mouse cardiomyocyte HL-1 cells showed that insulin regulates miR-29 family miRNAs (mir-29a, b and c) and improves cardioprotective MCL-1 levels in cardiomyocytes. [score:2]
Mild dysregulation of cardiac miR-29-MCL-1 axis in a hyperinsulinemic DM background (ZDF rat) does not show significant cardiac myofibril disorganization or loss. [score:2]
These observations suggest that Rap treatment causes severe dysregulation of the miR-29-MCL-1 axis in cardiac tissues of ZDF rat. [score:2]
Moreover, Rap treatment of young hyperinsulinemic ZDF rats caused severe dysregulation of cardiac miR-29-MCL-1 axis and myofibril bundle disorganization indicative of myocardial damage. [score:2]
These observations suggest that the myocardium of Rap -treated ZDF rats that had a further increase in miR-29 a, b and c miRNAs and further suppression of MCL-1 (Fig. 4E and 4F) compared to age-matched control rats, exhibited significant disorganization of myofibril bundles that reflect tissue damage. [score:2]
Regulation of diabetic marker miR-29 by insulin and rapamycin in mouse cardiomyocytes. [score:2]
They have mild to moderate dysregulation of miR-29-MCL-1 axis. [score:2]
These observations revealed that a miR-29-MCL-1 axis exists in cardiomyocytes. [score:1]
QTLs associated with the rat (rno)-miR-29 a/b cluster located on chromosome 4: 58,107,760-58,107,847 are shown (Taken from Rat RGSC3.4. [score:1]
Thus, the miR-29-MCL-1 axis is a major contributor to pancreatic dysfunction and T1DM. [score:1]
In this context, the diabetic marker microRNA miR-29 family that plays a role in increasing cell death is particularly noteworthy. [score:1]
RAP for miR-29 a, b, and c. The cardiac muscle cell line HL-1 (a generous gift from Dr. [score:1]
To determine how DM progression (natural or advanced by Rap treatment) caused dysregulation of cardiac miR-29-MCL-1 axis and promoted cardiomyocyte disorganization, we used male ZDF rats, a well-established rodent mo del for advanced DM [5], [6], [26], [27] and evaluated the correlation between regulation of miR-29-MCL-1 axis and disorganization of myofibril bundles in cardiac right ventricle. [score:1]
miR-29 is also one of the several miRNAs associated with inflammatory microvesicles [14]. [score:1]
In this study we used mouse atrial cardiomyocyte HL-1 cells and right ventricular tissues of ZDF rats to investigate how Rap modulates expression of miR-29-MCL-1 axis. [score:1]
The miR-29 family consists of miR-29 a, b (b1 and b2) and c that are located on two different chromosomes (chromosomes 4 and 13 in rat, 1 and 6 in mouse and 1and 7 in human) [7]. [score:1]
Further studies with primary cultures of cardiomyocytes from rat atrium and ventricle are needed to confirm that INS -mediated modulation of miR-29-MCL-1 axis is similar in atrial and ventricular cells. [score:1]
This study was undertaken to investigate whether insulin regulated the miR-29-MCL-1 axis in cardiomyocytes and if conditions that lead to progressive loss of insulin promote dysregulation of cardiac miR-29-MCL-1 axis and disorganization of cardiomyocytes. [score:1]
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[+] score: 232
In our current study, we found that in BMSCs, miR-29a-3p was able to directly target and suppress the expression of elastin. [score:8]
Interestingly, between the two miR-29a-3p -inhibited BMSC cultures, addition of bFGF -loaded PLGA NPs further upregulated elastin expression than free bFGF. [score:8]
These results indicated that inhibiting miR-29a-3p in the BMSCs not only upregulated intracellular expression of elastin, but also stimulated its extracellular secretion. [score:8]
For instance, during postnatal aortic development, miR-29 was found to be differentially expressed to downregulate elastin [14]. [score:7]
Expressions of miR-29a-3p (a), elastin mRNA (b), and elastin protein (c) were examined in BMSCs transduced with negative control inhibitor (control) or miR-29a-3p-specific inhibitor. [score:7]
MicroRNA-29a-3p inhibition resulted in upregulated expression and secretion of elastin in in vitro culture of BMSCs. [score:7]
We have previously demonstrated stable elastin -expressing bone marrow-derived mesenchymal stem cells (BMSCs) attenuated PFD in rats, and aim to further study the effect of microRNA-29a-3p regulation on elastin expression and efficacy of BMSC transplantation therapy. [score:6]
Twenty-four hours after these constructs were transfected into cells, together with miR-29a-3p, the activity of the luciferase fused with wild-type targeting sequence was significantly reduced, whereas the mutated version was practically unaffected (Fig.   2c), indicating that this site on the 3′-UTR of elastin mRNA was directly targeted by miR-29a-3p. [score:6]
Given the important regulatory role of miR-29a-3p in suppressing elastin expression, it will be of particular interest to our current work to investigate if miR-29a-3p is also differentially expressed in human PFD patients as well. [score:6]
Last but not least, in a very recent study [30], a comparison of miRNA expression profile between the dermis tissues of the young and elderly revealed that, several miRNAs, including miR-29, were upregulated in aged dermis. [score:6]
In cells haploinsufficient for elastin and in bioengineered vessels, inhibition of miR-29 could increase elastin expression levels [15]. [score:5]
Next, by stably inhibiting miR-29a-3p, expression and secretion of elastin are greatly elevated. [score:5]
Rats were assigned into six experimental groups (n = 12 each): (1) control, sham-operated rats to serve as healthy control; (2) PFD, vaginal distention was performed on the rats to induce PFD symptoms, and saline was injected 2 weeks after the operation; (3) BMSC (control) + bFGF, PFD rats were injected with control BMSCs and free bFGF 2 weeks after the operation; (4) BMSC (control) + PLGA-bFGF, PFD rats were injected with control BMSCs and bFGF -loaded PLGA 14 days after the operation; (5) BMSC (anti-miR-29) + bFGF, PFD rats were injected with miR-29a-3p -inhibited BMSCs and free bFGF 2 weeks after the operation; (6) BMSC (anti-miR-29) + PLGA-bFGF, PFD rats were injected with miR-29a-3p -inhibited BMSCs and bFGF -loaded PLGA 2 weeks after the operation. [score:5]
miR-29a-3p inhibition synergized with bFGF-PLGA in promoting the expression and secretion of elastin in differentiated BMSCs. [score:5]
In the current study, we further expand our work to utilize microRNA-29a-3p (miR-29a-3p), which was known to suppress elastin expression in various earlier reports [13– 16]. [score:5]
Four different in vitro cultures were established: (1) BMSC (control) + bFGF, control BMSCs with 20 ng/ml free bFGF; (2) BMSC (control) + bFGF-PLGA, control BMSCs with 20 ng/ml equivalent bFGF -loaded PLGA NPs; (3) BMSC (anti-miR-29) + bFGF, miR-29a-3p inhibited BMSCs with 20 ng/ml free bFGF; (4) BMSC (anti-miR-29) + bFGF-PLGA, miR-29a-3p -inhibited BMSCs with 20 ng/ml equivalent bFGF -loaded PLGA NPs. [score:5]
Inhibition of miR-29a-3p in BMSCs resulted in markedly higher expression and secretion of elastin, which consequently promoted the therapeutic potential of the BMSCs following injection into PFD rats. [score:5]
BMSCs transduced with negative control inhibitor (control) or miR-29a-3p-specific inhibitor were differentiated in the presence of either bFGF or bFGF-PLGA for 7 days. [score:5]
We found significantly higher expressions of elastin mRNA and protein in both groups of miR-29a-3p -inhibited BMSCs than control BMSCs, regardless of free bFGF or bFGF -loaded PLGA (Fig.   5a and b). [score:5]
In line with the above study by Li et al., as well as our previously work [12], inhibition of miR-29a-3p increased expression of elastin in BMSCs, which after being injected into PFD rats restored the function of tissues damaged by virginal distention. [score:5]
Using TargetScanHuman Release 7.1 online resource [18], we found a potential site in the three prime untranslated region (3′-UTR) of elastin mRNA matching the miR-29a-3p sequence (Fig.   2a). [score:5]
Fig. 3Constitutive inhibition of miR-29a-3p in BMSCs increased steady state expression level of elastin. [score:5]
As expected, both the mRNA and protein expressions of elastin were significantly elevated in miR-29a-3p -inhibited BMSCs compared to the control culture (Fig.   3b and c). [score:4]
In conclusion, we have demonstrated the role of miR-29a-3p as an important negative regulating factor of endogenous elastin expression in BMSCs. [score:4]
Fig. 1Flow cytometry identifies human BMSC -positive markers CD29, CD90, and CD105, but not negative marker CD45, on surface of the cells, against isotype antibody as control (shown in white) We continued to verify whether miR-29a-3p was able to directly target elastin in the isolated BMSCs. [score:4]
from the above studies consistently point to an important role of miR-29, miR-29a-3p in particular, in our current work, in regulating the expression of elastin in the mammalian system, including BMSCs. [score:4]
Downregulation of elastin by miR-29 family miRNAs has been wi dely reported. [score:4]
If this indeed is the case, depletion of miR-29a-3p in BMSCs should result in an upregulation of elastin. [score:4]
Fig. 1Flow cytometry identifies human BMSC -positive markers CD29, CD90, and CD105, but not negative marker CD45, on surface of the cells, against isotype antibody as control (shown in white) We continued to verify whether miR-29a-3p was able to directly target elastin in the isolated BMSCs. [score:4]
Recently in a study performed in vascular smooth muscle cells, miR-29 -mediated elastin downregulation was found to contribute to osteoblastic differentiation induced by inorganic phosphorus [16]. [score:4]
As expected, elastin secretion into the media was also consistently higher from both miR-29a-3p -inhibited BMSC cultures, with bFGF -loaded PLGA NPs exhibiting higher extent than free bFGF (Fig.   5c). [score:3]
a Sequence alignment of miR-29a-3p with potential targeting site in the 3′-UTR of elastin mRNA. [score:3]
In contrast, injection of miR-29a-3p inhibited BMSCs restored void volume and bladder void pressure (Fig.   7a and b, fifth and sixth columns). [score:3]
To test this hypothesis, inhibitor of miR-29a-3p was stably introduced in the cultured BMSCs (Fig.   3a). [score:3]
At last, by employing previously established bFGF -loaded PLGA nanoparticles to allow sustained release of bFGF, we demonstrate that injection of microRNA-29a-3p -inhibited BMSCs into PFD rats in vivo could significantly improve treatment outcome of urodynamic tests. [score:3]
However when injected together with the bFGF -loaded PLGA NPs, genetically engineered miR-29a-3p -inhibited BMSCs significantly improved results of urodynamic tests to comparable levels of the sham-operated control rats. [score:3]
In fact, transfection of miR-29a-3p into the BMSCs, after 24 hours, greatly repressed both the mRNA and protein expressions of endogenous elastin (Fig.   2d and e). [score:3]
In addition, co-injection of miR-29a-3p inhibited BMSCs together with bFGF -loaded PLGA fully reversed the defective peak bladder and leak point pressures (Fig.   7a and b, sixth column). [score:3]
[##] P < 0.01 vs BMSC (control) + bFGF-PLGA and BMSC (anti-miR-29) + bFGF We next established a rat PFD mo del to test the effect of miR-29a-3p -inhibited BMSC transplantation on PFD symptoms in vivo. [score:3]
d and e Expressions levels of elastin mRNA (d) and protein (e) were examined in BMSCs transfected with miR-NC or miR-29a-3p. [score:3]
Noteworthy, the bFGF sustained release from the PLGA NPs was able to support the continuous proliferation of cells even for prolonged incubation beyond day 5. Therefore consistent with our previous work, bFGF -loaded PLGA NPs sustained release system was also effective for our genetically engineered miR-29a-3p -inhibited BMSCs. [score:3]
We inhibited endogenous microRNA-29a-3p in BMSCs and investigated its effect on elastin expression by RT-PCR and. [score:3]
The MISSION Lenti hsa-miR-29a-3p Inhibitor Kit (HLTUD0434) and negative control (HLTUD001C) was purchased from Sigma-Aldrich, and was packaged for transduction to create stable cell lines according to the manufacturer’s instructions. [score:3]
After co-injection with PLGA -loaded bFGF NP into the PFD rats in vivo, microRNA-29a-3p -inhibited BMSCs significantly improved the urodynamic test results. [score:3]
bFGF -loaded PLGA NP promoted the proliferation of miR-29a-3p -inhibited BMSCs. [score:3]
We first validate that elastin is indeed targeted and repressed by miR-29a-3p in isolated human BMSC culture. [score:3]
Importantly in rats receiving injections of miR-29a-3p -inhibited BMSCs, the decreased void volume and bladder void pressure were both rescued (Fig.   6b and c, fifth and sixth columns), with defects in BMSC (anti-miR-29) + bFGF-PLGA group rats almost completely restored to similar levels of the sham-operated control rats (Fig.   6b and c, sixth column). [score:3]
miR-29a-3p inhibition synergized with bFGF-PLGA in improving urodynamic tests in rat PFD mo del. [score:3]
[**] P < 0.01, ns not significant vs miR-NC The above results suggested that miR-29a-3p was a bona fide negative regulator of elastin in BMSCs. [score:2]
[**] P < 0.01, ns not significant vs miR-NC The above results suggested that miR-29a-3p was a bona fide negative regulator of elastin in BMSCs. [score:2]
MiR-29a-3p targets elastin in BMSCs. [score:2]
MiR-29a-3p expression was determined with TaqMan Advanced miRNA Assay Kit (478587_mir, Applied Biosystems, Waltham, MA, USA) according to the manufacturer’s instructions. [score:2]
[$] P < 0.05 vs PFD, BMSC (control) + bFGF, BMSC (control) + bFGF-PLGA and BMSC (anti-miR-29) + bFGF from the LPP test displayed a very similar pattern. [score:1]
The MISSION miR-29a-3p mimic (HMI0434) and miR negative control (HMC0002) were purchased from Sigma-Aldrich (St. [score:1]
Values were mean ± SD from three independent experiments We next evaluated the effect of the released bFGF on proliferation of the miR-29a-3p -inhibited BMSCs (Fig.   4b). [score:1]
[$] P < 0.05 vs PFD, BMSC (control) + bFGF, BMSC (control) + bFGF-PLGA and BMSC (anti-miR-29) + bFGF Results from the LPP test displayed a very similar pattern. [score:1]
We next investigated the effect of miR-29a-3p inhibition, when combined with bFGF-PLGA NPs, on the differentiation of BMSCs. [score:1]
b Cell proliferation was measured by, after empty PLGA, free bFGF without PLGA (bFGF), or bFGF -loaded PLGA (bFGF-PLGA) were added into the culture of miR-29a-3p -inhibited BMSCs. [score:1]
[$$] P < 0.01 vs PFD, BMSC (control) + bFGF, BMSC (control) + bFGF-PLGA and BMSC (anti-miR-29) + bFGF Taken together, regardless of bFGF source, transplant of control BMSCs did not exhibit any alleviating effect on the PFD rats. [score:1]
[$$] P < 0.01 vs PFD, BMSC (control) + bFGF, BMSC (control) + bFGF-PLGA and BMSC (anti-miR-29) + bFGF Taken together, regardless of bFGF source, transplant of control BMSCs did not exhibit any alleviating effect on the PFD rats. [score:1]
Values were mean ± SD from three independent experiments We next evaluated the effect of the released bFGF on proliferation of the miR-29a-3p -inhibited BMSCs (Fig.   4b). [score:1]
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[+] score: 228
Conversely, upregulation of miR-29 levels was observed after stimulation of HSC with the antifibrotic mediator HGF (Figure 8), previously shown to inhibit expression of various collagens [21], [48], [49]. [score:8]
Upregulation of miRNA-29 by HGF and downregulation by TGF-β take part in the anti- or profibrogenic response of HSC, respectively. [score:7]
Indeed, our in vitro data reveal a definite inhibition of collagen type IV, that is the most upregulated collagen form in the fibrotic liver [6], by miR-29. [score:6]
Whereas TGF-β stimulation leads to decreased miR-29 levels, but to pronounced upregulation of collagen synthesis, HGF stimulation leads to elevated miR-29 expression, but to repression of collagen synthesis. [score:6]
However, overexpression of miR-29 in myofibroblastic HSC did not affect the expression of SMA (Figure S1 D). [score:5]
Thus, whereas col1A2 and col4A1 collagen expression was highly increased in myofibroblastic HSC, the levels of miR-29a were suppressed (Figure 3 A, B). [score:5]
Together, these data demonstrated that miR-29 specifically inhibits transcription and protein expression of collagen I and IV. [score:5]
After demonstrating that repression of the collagen-inhibiting miR-29 is an important downstream TGF–β effect, we studied if miR-29 overexpression can overcome the profibrogenic features mediated by TGF-β such as col1A1 induction. [score:5]
TGF-β treatment resulted in highly increased col1A1 expression in HSC cells treated with scrambled miRNA or with antago-miR-29, but only a moderate col1A1 induction in miR-29 overexpressing HSC after transfection with ago-miR-29. [score:5]
miR-29a expression in HSC after 3 days (3d) of primary culture (A) and miR-29a and miR-29b expression in myofibroblastic HSC-T6 (B). [score:5]
Therefore, miR-29 expression appears to be reciprocally regulated by profibrogenic (TGF-β) and antifibrogenic growth factors (HGF) in HSC, suggesting that miR-29 occupies a central role in responding to the antagonistic actions of HGF and TGF-β in regulating collagen synthesis in activated and transdifferentiated HSC. [score:5]
Interestingly, the expression of mature miR-29a, but not of miR-29b, was contrary to the collagen expression during myofibroblastic transition. [score:5]
0024568.g008 Figure 8 miR-29a expression in HSC after 3 days (3d) of primary culture (A) and miR-29a and miR-29b expression in myofibroblastic HSC-T6 (B). [score:5]
In contrast, the incubation of primary and transdifferentiated HSC with the recombinant hHGF elicited a marked upregulation of the miR-29a/b levels (Figure 8). [score:4]
Interestingly, our findings proved that upregulation of miR-29a efficiently can overcome the profibrogenic influence of TGF-β on collagen synthesis (Figure 9). [score:4]
In agreement with the data on rat HSC, miR-29 is repressed by TGF-β, but upregulated by HGF (Figure S2). [score:4]
miR-29a and miR-29b are downregulated during experimental liver fibrosis in rat. [score:4]
Transfection of HSC with miR-29a mimics lead to a 10-fold overexpression of miR-29a. [score:3]
Reduced miR-29a and miR-29b expression in livers after BDO. [score:3]
While miR-29 and HGF expression was significantly reduced (C,D), hydroxyproline and collagen mRNA were signifcantly increased in BDO livers (B) (*: p<0.05 **:p<0.01; ***: p<0.001). [score:3]
Since miR-29 is thought to be involved in modulating expression of extracellular matrix components (Table S3) [30], [31], [32], [34], this makes them promising candidates for collagen I and IV repression after HGF stimulation of HSC. [score:3]
Keeping with the antifibrotic function of miR-29, miR-29 is reduced in liver biopsies after liver intoxication in mice and after chronic liver disease in humans [35]. [score:3]
In HSC that express low levels of miR-29a due to transfection with scrambled miRNA or with a miR-29a silencer, TGF-β treatment highly induced col1A1 synthesis. [score:3]
Figure S2 miR-29 expression in human skin fibroblasts after stimulation with HGF. [score:3]
Thus, whereas TGF-β stimulation leads to a reduction in miR-29 expression and de-repression of collagen synthesis, stimulation with HGF was definitely associated with highly elevated miR-29 levels and markedly repressed collagen-I and -IV synthesis. [score:3]
In order to analyze if other features of myofibroblastic transition were affected by miR-29, we determined SMA expression in miR-29 treated HSC, because increased SMA assembly is one of the most important features of myofibroblastic transition (Figure S1 A). [score:3]
Hence, miR-29a/b overexpression in HSC resulted in a marked reduction of collagen-I and -IV synthesis. [score:3]
Stimulation of primary HSC and myofibroblastic HSC-T6 cells with TGF-β decreased significantly the expression of miR-29a and miR-29b in vitro (Figure 8). [score:3]
Diminished effect of TGF-β on col1A1 expression in miR-29 treated HSC. [score:3]
Insertion of the miR-29 binding sites (wt), but not with mutated binding site (mu), resulted in reduced reporter gene expression by miR-29a treated HSC (A–D). [score:3]
Overexpression of miR-29 can overcome TGF-β mediated induction of col1A1. [score:3]
Indeed, insertion of the 3′-UTR of col4A1 and col4A5 downstream of the luciferase reporter gene lead to a reduction in luciferase expression after treatment of HSC with ago-miR-29a, mimicking miR-29a (Figure 4). [score:3]
Table S3 Ranking list of putative collagen targets from miR-29*. [score:3]
Therefore, in addition to collagen-1, the collagen-4 mRNA could be an important target of miR-29 in HSC after HGF stimulation. [score:3]
Next, we induced experimental fibrosis by bile duct occlusion (BDO) in rats and studied the miRNA-29 expression during liver fibrogenesis. [score:3]
Furthermore, transfection of ago-miR-29a and ago-miR-29b into HSC suppressed transcription and protein synthesis of collagen type I and IV ((Figure 6A, B). [score:3]
Thus, our findings convincingly demonstrate that HGF mediates antifibrotic signals by influencing miR-29 expression and thereby counteracting the profibrotic activity of TGF-β. [score:3]
Analysis of the transcriptional levels of the primary precursor miRNA (pri-miRNA) revealed that pri-miR-29b/c transcript levels are only moderately suppressed, but that the miR-29a/b gene of chromosome 7 undergoes predominant transcriptional repression upon myofibroblastic transition of HSC. [score:3]
Reciprocal expression of the collagen subunits, col1A1 and col4A2, and primary and mature miR-29. [score:3]
Consistent with the antifibrogenic and inhibitory function of miR-29 in collagen I and IV synthesis and the increase of col1A2 and col4A2 (Figure 7 B), we observed a significant reduction in hepatic miR-29a and miR-29b levels in this experimental BDO mo del (Figure 7 C). [score:3]
Contrary effects of HGF and TGF-β on miR-29 expression in HSC. [score:3]
However, col1A1 induction by TGF-β was only marginal in HSC, that highly overexpress miR-29a after transfection with miR-29a mimics (Figure 9). [score:3]
Hepatology 36 Mott JL Kurita S Cazanave SC Bronk SF Werneburg NW 2010 Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB. [score:3]
Among the putative miR-29 binding sites of the collagen mRNA (shown in the Table S4), the following sites were chosen for our further analyses, due to the suggestions of Bartel et al. [50] to function most likely as an inhibitory miR-29 interaction sequence: the region of positon 29–35 in the col4A1 3′-UTR, of postion 404–410 in the col4A5, positon 903–909 in the col1A1, and of position 506–512 in the col1A2 3′-UTR (Table S4). [score:3]
miR-29 synthesis in HSC is suppressed by TGF-β, but promoted by HGF. [score:3]
In the present study, we now collect evidence that in response to the counteracting HGF / TGF-β signals the miR-29 levels in HSC are contrarily regulated. [score:2]
To demonstrate the specificity of miR-29 for the binding sites, in the 3′-UTRs two point mutations were incorporated to abolish the putative miR-29 recognition sequences of the collagen-4 mRNA (col4A1, col4A5) and collagen-1 transcripts (col1A1 and col1A2). [score:2]
These findings are in agreement with the data of Du et al. [33] and recent reports showing the miR-29 regulation of elastin, fibullin and collagen I synthesis [30], [31], [32], [34], [35]. [score:2]
The interaction of miR-29 with 3′-untranslated mRNA regions (UTR) was analyzed by reporter assays. [score:2]
miR-29a and miR-29b regulate collagen I and IV synthesis in activated HSC. [score:2]
Transfection of HSC-T6 with ago-miR-29a or ago-miR-29b did not result in altered SMA expression when compared to scrambled miRNA treated HSC-T6 cells. [score:2]
Putative miR-29 binding sites in the collagen col1A1 (A), col1A2 (B), col4A1 (C) and col4A5 (D) 3′-UTR (wt) and the corresponding mutated sequences (mu) carrying two point mutations (bold and underlined) were cloned into psiCHECK [TM]-2 vector. [score:2]
0024568.g005 Figure 5Putative miR-29 binding sites in the collagen col1A1 (A), col1A2 (B), col4A1 (C) and col4A5 (D) 3′-UTR (wt) and the corresponding mutated sequences (mu) carrying two point mutations (bold and underlined) were cloned into psiCHECK [TM]-2 vector. [score:2]
Interaction of miR-29a with the binding regions of col1A1, col1A2, col4A1 and col4A5 3′-UTR transcripts. [score:1]
Repression of collagen synthesis by miR-29a and miR-29b. [score:1]
Co-transfection of HSC-T6 with the reporter plasmids and ago-miR-29a reduced reporter activity of the wild type controls, but not of the mutated collagen type I and IV constructs (Figure 5 A–D). [score:1]
Strikingly, all of the collagen-1 and -4 transcripts contained binding sites for members of the miRNA-29 family in their 3′UTR (Table 1). [score:1]
Furthermore, our in vitro and in vivo studies on HSC or on BDO -treated fibrotic livers, respectively, suggest that the loss of miR-29 in HSC after TGF-β exposure and during liver fibrogenesis leads to the abolishment of collagen type I and IV repression. [score:1]
For this purpose, HSC-T6 cells were transfected with miR-29a mimics (ago-miR29a) in comparison to scrambled or miR-29-silencing miRNA (antago-miR-29). [score:1]
We therefore studied the influence of HGF and TGF-β on the miR-29 collagen axis in HSC. [score:1]
Recently, miR-29 has been reported to be involved in ECM synthesis. [score:1]
0024568.g009 Figure 9 The myofibroblastic HSC-T6 cells were transfected with scrambled miRNA, miR-29 mimic (ago-miR-29), or with a miR-29 silencer (antago-miR-29). [score:1]
miR-29 interaction with the 3′-UTR of col4A1 and col4A5 transcripts. [score:1]
The synthesis of extracellular matrix proteins is modulated by microRNA-29 (miR-29) in extrahepatic tissue [30], [31], [32], [33]. [score:1]
miRNA mimicking miR-29a, miR-29b and a scrambled miRNA control were obtained from Dharmacon (Lafayette, USA). [score:1]
The miR-29 family consists of miR-29a, miR-29b (b [1], b [2]), and miR-29c, which differ in only two or three nucleotides, respectively. [score:1]
Thus, miR-29a is able to lower significantly the profibrogenic features of TGF-β in collagen induction. [score:1]
HSC were not stimulated (−) or treated (+) with either TGF-β or hHGF and miR-29a/b levels were determined by Real Time-PCR analysis. [score:1]
0024568.g006 Figure 6 mRNA quantification of collagen subunits in HSC treated either with miR-29a, miR-29b (ago-miR-29a, ago-miR-29b), or scrambled miRNA by Real-Time PCR (A). [score:1]
Additionally, miR-29a and miR-29b levels (C) and HGF and c-met transcripts (D) were quantified by Real-Time PCR. [score:1]
Thus, our data provide detailed evidence for the antifibrotic action of miR-29 in response to HGF signalling that is counteracted by the profibrotic growth factor TGF-β. [score:1]
Recent reports suggest that miR-29 is also involved in the synthesis of collagen type I in liver fibrosis [34], [35]. [score:1]
0024568.g003 Figure 3 RNA of primary HSC in the quiescent stage (day 3 of primary culture) and after myofibroblastic activation (day 7 of primary culture) was analyzed for mRNA col1A2 and col4A1 levels (A), as wells as for the levels of mature miR-29a and miR-29b (B), and the primary transcripts of the miR-29a/b and miR-29b/c gene (C). [score:1]
In order to study miR-29 function in collagen synthesis, we inserted the 3′-UTR sequences downstream of a luciferase reporter (Figure 4 A). [score:1]
RNA of primary HSC in the quiescent stage (day 3 of primary culture) and after myofibroblastic activation (day 7 of primary culture) was analyzed for mRNA col1A2 and col4A1 levels (A), as wells as for the levels of mature miR-29a and miR-29b (B), and the primary transcripts of the miR-29a/b and miR-29b/c gene (C). [score:1]
Conversely, a decrease in miR-29 levels is observed during collagen accumulation upon experimental fibrosis, in vivo, and after TGF-β stimulation of HSC, in vitro. [score:1]
The myofibroblastic HSC-T6 cells were transfected with scrambled miRNA, miR-29 mimic (ago-miR-29), or with a miR-29 silencer (antago-miR-29). [score:1]
Reporter plasmids were cotransfected into HSC-T6 in combination with scrambled miRNA or miR-29a mimic (ago-miR-29a), respectively, and luciferase reporter expression was determined by the hRluc luminescence measurement normalized to firefly luminescence (hluc+) (B–C). [score:1]
The repressive effect of miR-29 on collagen synthesis was studied in HSC treated with miR-29 -mimicks by Real-Time PCR and immunoblotting. [score:1]
The genes for miR-29a and miR-29b [1] are both located on chromosome 7, whereas the genes for miR-29c and miR-29b [2] are located on chromosome 1. Each gene pair is transcribed in tandem resulting in a common pri-miRNA from which the mature miR-29 members are released after further processing [36], [37]. [score:1]
We demonstrate that miR-29 is not only involved in collagen type I but also in type IV synthesis of myofibroblastic HSC. [score:1]
The 3′-UTR of the collagen-1 and −4 subtypes were identified to bind miR-29. [score:1]
Then, the levels of TGF-β, HGF, collagen-I and -IV mRNA, in addition to miR-29a and miR-29b were determined after HGF and TGF-β stimulation of HSC or after experimental fibrosis induced by bile-duct obstruction in rats. [score:1]
miR-29a levels were determined by Real Time-PCR analysis. [score:1]
The importance of miR-29 in hepatic collagen homeostasis is underlined by our in vivo data that shows the lack of miR-29 in severe experimental fibrosis after bile duct obstruction. [score:1]
This loss of miR-29 is suggested to be due to the response of HSC to exposure to profibrogenic mediators as shown by our in vitro findings on TGF-β stimulated HSC. [score:1]
The level of miR-29 transfected into HSC-T6 cells was analyzed by Real-Time PCR, demonstrating stable levels between 8 h and 48 h post-transfection. [score:1]
This loss of the miR-29a and miR-29b in fibrotic BDO treated livers is attended by reduced levels of HGF upon fibrosis (Figure 7 D). [score:1]
In this respect, the members of the miR-29 family are the most promising candidates because they are repressed during myofibroblastic transition and they hold highly conserved binding sites in the 3′-UTR of the various subunits of collagen 1 and 4 (Table 1). [score:1]
mRNA quantification of collagen subunits in HSC treated either with miR-29a, miR-29b (ago-miR-29a, ago-miR-29b), or scrambled miRNA by Real-Time PCR (A). [score:1]
The reduced levels of miR-29 during fibrosis are associated with an increase of extracellular miR-29 in serum depending on the fibrotic stage (manuscript in preparation). [score:1]
The reporter plasmids were co -transfected into HSC-T6 cells with either scrambled miRNA or miR-29a mimic (ago-miR-29a), respectively. [score:1]
Table S4 Putative binding sites of the members of the miR-29 family to the 3′-UTR of different collagens. [score:1]
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[+] score: 175
This was demonstrated by the data of ChIP which showed a directly targeting miR-29 promotor by p65 and result of cells incubated NF-κB inhibitor, BAY 11-7082 that leaded to abolishment of high glucose -induced upregulation of miR-29 expression. [score:11]
By luciferase reporter assays and expression analysis of Keap1 in HK [miR−29 mimic] or HK [miR−29 inhibitor] cells, we can draw a conclusion of miR-29 directly regulated Keap1 expression by targeting Keap1 mRNA 3′ UTR. [score:10]
cell treated with 45 mM + DMSO Detection of abnormal expression of miR-29 and Keap1 in HK-2 cell lead us to determine whether miR-29 directly regulates Keap1 expression. [score:7]
This finding demonstrated a novel mechanism by which high glucose causes renal tubules injury and may provide insight as to what might be acted as therapy target by providing evidence supporting a role for miR-29 overexpression in the inhibition of Keap1/Nrf2 pathway. [score:7]
By result of western blotting, we observed that high glucose induced upregulation of Keap1 and downregulation of nuclear Nrf2 was abrogated by miR-29 mimic treatment (Fig.   6b). [score:7]
a Cells were transfected with miR-29 mimic and b miR-29 inhibitor as well as respective negative control (NC) for 48 h; miR-29 level, translational activity of Keap1 and expression of Keap1 mRNA and protein were determined. [score:7]
In diabetic rat, miR-29 was downregulated and its expression is negatively correlated with both of serum creatinine and creatinine clearance. [score:6]
In this present study, we observed that NF-κB activity was enhanced mediated by high glucose induced reduction of deacetylases activity of Sirt1, which leaded to downregulation of miR-29 and inhibition of Keap/Nrf2 signal. [score:6]
Relative protein band density was quantified by image J. To achieve alteration of expression of miR-29, cells were treated with miR-29 mimic or inhibitor with the negative control (NC) of nonsense strand using Lipofectamine (Invitrogen). [score:5]
We altered miR-29 expression by cell incubated with miR-29 mimic or inhibitor. [score:5]
NF-κB was demonstrated to regulate miR-29 expression by directly binding to its promotor. [score:5]
This data suggested an expressional regulation of miR-29 by NF-κB. [score:4]
While high glucose induced down regulation of miR-29 contributed to enhancement of Keap1 expression that finally reduced Nrf2 content by ubiquitinating Nrf2. [score:4]
This was further confirmed by qRT-PCR assay which showed that inhibition of NF-κB pathway by BAY 11-7082 treatment increased miR-29 expression in high glucose-triggered cell. [score:4]
Fig.  4NF-κB regulates miR-29 expression in high glucose-triggered HK-2 cells. [score:4]
Additionally, overexpression of miR-29 effectively relieved high glucose-reduced cell viability. [score:3]
One day later, cells were co -transfected with pGL4-TK-Luc-Keap1 (0.5 μg) with control of pGL-SV40 (internal control, 0.018 μg) and miR-29 mimic or inhibitor. [score:3]
b Western blot was performed to analyze expression of Keap1 and nuclear Nrf2 in 5.5 mM and 45 mM glucose-triggered HK-2 [miR−29mimic] cells To determine the role of miR-29 on high glucose triggered cell, cell viability was examined in HK-2 [miR−29 mimic] cell. [score:3]
Calculated Keap1 mRNA expression levels were normalized to the expression levels of GAPDH and relative miR-29 level was normalized to U6 of the same cDNA sample. [score:3]
Renal tubule was obtained from rats treated with STZ for 4, 8, 12, 16 weeks and lyzed for analysis of miR-29 expression. [score:3]
Overexpression of miR-29 enhanced cell viability. [score:3]
Notably, decreased expression of miR-29 by NF-κB signal has been described in cells and tissues [12, 13]. [score:3]
Due to description of decreased expression of miR-29 by NF-κB signal in cells and tissues [12, 13], we speculated that NF-κB/miR-29 axis might be involved in high glucose incubated renal cell. [score:3]
Level of miR-29 was significantly downregulated in cells incubated with 30 and 45 mM high glucose compared with cell treated with 5.5 mM normal glucose (Fig.   2c). [score:3]
As shown in Fig.   5b, level of miR-29 declined by 10 fold, binding activity of miR-29 and Keap1 promotor was boosted that leads to increase of the expression of Keap1 mRNA and protein. [score:3]
We attempted to figure out the target gene for miR-29. [score:3]
The data showed that high glucose promoted ubiquitination of Nrf2 whereas this promotion was reversed by overexpression of miR-29 (Fig.   6a). [score:3]
The data of luciferase assay showed that miR-29 directly targets to Keap1 mRNA. [score:3]
The correlation analysis demonstrated that abnormal miR-29 expression is negatively related to serum creatinine (Spearman correlation is −0.96, P = 0.000; Fig.   1d) and creatinine clearance (Spearman correlation is −0.93, P = 0.000; Fig.   1e). [score:3]
c miR-29 expression was determined. [score:3]
Fig.  7Effect of overexpression of miR-29 on cell viability in glucose-triggered HK-2 cell. [score:3]
b Cells were exposed to BAY 11-7082 for 2 h before 5.5 and 45 mM glucose treatment and miR-29 expression was determined. [score:3]
MiR-29 directly regulates Keap1. [score:2]
Fig.  6Ubiquitination of Nrf2 was regulated by miR-29/Keap1 axis in high glucose triggered HK-2 cells. [score:2]
In HK-2 [miR−29 mimic] cell, level of miR-29 was significantly increased by 12.9 fold, binding activity of miR-29 and Keap1 promotor was reduced and expression of Keap1 mRNA and protein was attenuated compared with pre-NC incubated cell (Fig.   5a). [score:2]
cell treated with 45 mM + pcDNA was performed to assess whether NF-κB directly binds to miR-29 gene in high glucose cultured HK-2 cell. [score:2]
The ChIP assay was carried out to detect the possible target miR-29 gene by p65. [score:2]
All cells were incubated with glucose for 48 h. To evaluate whether NF-κB regulates miR-29 expression in high glucose incubated HK-2 cell, the cells were pretreated with BAY11-7082 (5 μmol/L) (Sigma-Aldrich Co. [score:2]
These data indicated that miR-29 is involved in pathological process of diabetes and might function as one of modulatory factors. [score:1]
Renal tubular was obtained for detection of miR-29 level. [score:1]
As shown in Fig.   7, reduction of cell viability by high glucose was effectively enhanced by miR-29 mimic treatment. [score:1]
Among these, miR-29 is observed in diabetic patients [10] and also ameliorates hyperglycemia -induced renal dysfunction [11]. [score:1]
Notably, both miR-29 and NF-κB activity play vital roles in high glucose induced decrease of cell viability. [score:1]
pre-NC or NC To determine the downstream molecule of miR-29/Keap1 axis, we examined Nrf2, a nuclear transcriptional factor that commonly activated by Keap1, in 45 mM high glucose-triggered HK-2 [miR−29 mimic] cell. [score:1]
cell treated with 45 mM + pcDNA Chip assay was performed to assess whether NF-κB directly binds to miR-29 gene in high glucose cultured HK-2 cell. [score:1]
The data showed that miR-29 level was decreased in time -dependent manner after rat mo del of diabetes established (Fig.   1c). [score:1]
Level of microR-29 (miR-29) was assessed using quantitative RT-PCR. [score:1]
We made a prediction of the possible binding site in Keap1 3′ UTR by miR-29 and this was demonstrated by online bioinformatics analysis (data is not shown). [score:1]
Thus we speculated that NF-κB/miR-29 axis might be involved in high glucose incubated renal cell. [score:1]
Acetyl-p65 HK-2 miR-29 Nrf2 Serum creatinine Diabetes mellitus is a common metabolic disorder which is associated with chronic complications such as angiopathy, retinopathy, and peripheral neuropathy. [score:1]
In summary, our data suggested that high glucose induced renal tubular injury might be a process of a signal transduction pathway of Sirt1/NF-κB/miR-29/Keap1/Nrf2. [score:1]
Combination of p65 and miR-29 promotor was assessed using chromatin immunoprecipitation. [score:1]
NF-κB binds to miR-29. [score:1]
High glucose promotes ubiquitination of Nrf2 via miR-29/Keap1 axis. [score:1]
As shown in Fig.   4a, high glucose promoted association between p65 and miR-29 promotor in a manner of time dependent. [score:1]
To assess the correlation between the serum creatinine or blood urea nitrogen (BUN) and serum miR-29 level, the Spearman correlation coefficient was used. [score:1]
a Cells were stimulated with 5.5 and 45 mM glucose for 12, 24, 48 h and combination of p65 and miR-29 gene was examined using. [score:1]
Correlated analysis was performed to assess relationship between d miR-29 level and Serum creatinine as well as e miR-29 level and creatinine clearance. [score:1]
[1 to 20 of 58 sentences]
6
[+] score: 167
Taken together, the present study shows that bladder outlet obstruction, such as that seen in elderly men with enlarged prostate glands, leads to reduced expression of miR-29b and miR-29c in the bladder and that this is associated with increased expression of miR-29 targets, including the matrix proteins elastin and Sparc. [score:7]
Human detrusor cells were transfected with miR-29c inhibitor and eight validated miR-29 targets, most of which were represented among the top 50 predicted targets in Figure 3A, were examined using western blotting. [score:7]
We also demonstrate that genetic depletion of miRNAs, including miR-29, increases bladder elastin expression and stiffness independently of outlet obstruction and that miR-29 inhibitor transfection in vitro replicates several of the expression changes associated with miR-29 repression in outlet obstruction. [score:7]
Together, these circumstances may well explain the more widespread apparent impact of miR-29 repression in outlet obstruction (8/8 examined target proteins increased) compared to inhibitor transfection (4/8 examined target proteins increased). [score:6]
Four of the eight selected miR-29 targets, including Eln (elastin or tropoelastin), Fos (also known as c-Fos), Sparc (osteonectin) and sprouty homolog 1 (Spry1), were significantly increased following inhibitor transfection (Figure 3D, left row). [score:5]
To address the functional impact of miR-29, we transfected a miR-29 inhibitor and mimic in vitro and conditionally deleted Dicer in vivo [5] and examined the effect of these interventions on tropoelastin expression and on tissue mechanical properties. [score:5]
Currently, we can only speculate on the role of these proteins in outlet obstruction, but it is of considerable interest that the miR-29 target Spry1 [14], which is an established ERK1/2 inhibitor [49], increases after prolonged outlet obstruction. [score:5]
For tropoelastin, whose mRNA correlated inversely and significantly with miR-29 in outlet obstruction, we found that transfection of a miR-29c inhibitor resulted in increased tropoelastin expression. [score:5]
Of the 30 miRNAs that are highly expressed in the mouse detrusor [5, 41] none except miR-29 is predicted to target tropoelastin. [score:5]
Some predicted and confirmed miR-29 targets, including Fbn1, which is an integral part of the elastic fiber meshwork, and Lamc1, a protein present in the basement membrane, were increased in outlet obstruction but were not significantly affected at the protein level following inhibitor transfection (not shown). [score:5]
Additional regulatory inputs on miR-29 expression include c-Myc and NF-κB [11], and recent work has provided considerable insight into c-Myc -mediated repression, which appears to depend on a repressor complex consisting of c-Myc, histone deacetylae 3 (Hdac3) and enhancer of zeste homologue 2 (Ezh2) [18]. [score:4]
Detrusors from smooth muscle-specific Dicer knockout mice were used to examine if reduction of miR-29 in vivo increases tropoelastin expression. [score:4]
The extracellular matrix molecule elastin is one of the best established targets of miR-29, and its message has 14 binding sites dispersed over the coding sequence and the 3’UTR [12]. [score:3]
Repression of miR-29 after outlet obstruction is associated with increased levels of miR-29 target proteins. [score:3]
Outlet obstruction and transforming growth factor β (TGF-β1) stimulation leads to reduced expression of miR-29. [score:3]
0082308.g005 Figure 5(A) Western blots for eight miR-29 targets in sham-operated control bladders and at 6 weeks of obstruction. [score:3]
We also examined if the reduction of miR-29 correlated with altered miR-29 target mRNAs, including tropoelastin and Sparc. [score:3]
6 weeks) of the top 50 mRNA targets of miR-29 when miR-29 was repressed at 10 days and when miR-29 recovered after de-obstruction (c. f. Figure 2A and B). [score:3]
sham) of miR-29 target messenger RNAs (mRNA; black circles) and proteins (white circles). [score:3]
Considerably more time was moreover allowed for de-repression of miR-29 targets in the in vivo setting (6 wk vs. [score:3]
It may be argued that a miRNA other than miR-29 is responsible for altered tropoelastin expression in Dicer KO bladders. [score:3]
Outlet obstruction and TGF-β reduce miR-29 expression. [score:3]
This revealed a pronounced increase around individual cells and around muscle bundles in obstructed bladders, consistent with its increased mRNA level and with the fact that it is a miR-29 target [48]. [score:3]
We next set out to determine miR-29 expression. [score:3]
Real-time quantitative PCR to confirm reduced expression of miR-29. [score:3]
The experimental support for an impact of miR-29 on protein synthesis in the bladder following outlet obstruction extends well beyond a significant correlation between miR-29b/c and target mRNAs. [score:3]
We next tested whether TGF-β1 reduces miR-29 expression using cultured smooth muscle cells from human bladder. [score:3]
Repression of miR-29 during outlet obstruction is associated with increased levels of miR-29 target messenger RNAs (mRNAs). [score:3]
The matricellular protein Sparc is a confirmed miR-29 target [13] that influences collagen fibril morphology and function [47]. [score:3]
Bladder outlet obstruction increases miR-29 target protein levels. [score:3]
Type I and type III collagens are however established targets of miR-29 [10], and their mRNAs were largely unchanged at 10 days and at 6 weeks (Col1a1 at 10 days: up by 15%, q=2.7, p=0.05; Col3a1 at 10 days: up by 12%, q=8.7, p=0.12). [score:3]
Unlike other miRNAs, miR-29 also targets a large battery of collagens, including collagens I and III [10]. [score:3]
This would repress miR-29, and hence it would be more difficult to see an effect of miR-29 inhibition. [score:3]
Our studies support a mo del in which multiple signaling pathways converge on repression of miR-29 in outlet obstruction, facilitating matrix protein expression and leading to altered mechanical properties of the urinary bladder. [score:3]
MiR-29 target mRNAs change in outlet obstruction. [score:2]
Thus, several independent lines of evidence support a regulatory role of miR-29 in tropoelastin synthesis in the bladder, consistent with the large number of miR-29 binding sites in its mRNA [10, 12]. [score:2]
Several of the miR-29 targets that we studied, including Col15a1, Tdg and Spry1, have not been considered previously in the context of hypertrophic growth and remo deling of the bladder. [score:2]
SMAD proteins belong to a conserved family of TGF-β signal transducers that are regulated by phosphorylation [17], and the repression of miR-29 by TGF-β was shown to involve SMAD3 [16]. [score:2]
The matricellular protein Sparc has three miR-29 binding sites clustered in its proximal 3’ UTR, and, similar to elastin, this protein is effectively regulated by miR-29 in vitro [13]. [score:2]
Our starting hypothesis was that TGF-β/SMAD3 signaling would repress miR-29 in outlet obstruction. [score:1]
Figure S2 Flow chart showing the mo del proposed for miR-29 repression in outlet obstruction and for miR-29 -mediated matrix remo deling and altered passive mechanical properties. [score:1]
The reduced level of miR-29 leads to increased levels of mRNAs encoding extracellular matrix proteins (3), including elastin and Sparc (osteonectin), but possibly also collagens and fibrillin-1. The resulting protein synthesis and matrix deposition (4) leads to increased detrusor stiffness (5) (and increased elastic modulus) which counteracts (6) further distension. [score:1]
Together, these findings support the view that repression of miR-29, independent of surgical obstruction of the urethra, leads to matrix remo deling. [score:1]
We therefore hypothesized that outlet obstruction leads to SMAD3 phosphorylation repressing miR-29, and that this in turn has an impact on protein synthesis and mechanical properties of the bladder. [score:1]
c-Myc -mediated repression of miR-29 involves a complex consisting of c-Myc (Myc), histone deacetylase 3 (Hdac3) and enhancer of zeste homolog 2 (Ezh2) which binds to conserved sequences in the promoters of the miR-29a/b1 and miR-29b2/c genes [18]. [score:1]
Studies using cultured cells support the idea that transforming growth factor-β (TGF-β), a central mediator in fibrogenesis, represses miR-29 [16]. [score:1]
sham), a time point when miR-29 was reduced (c. f. Figure 2A and B). [score:1]
The miR-29 cluster has gained recognition as a modulator of extracellular matrix production [7- 10]. [score:1]
This hypothesis was based on a handful of prior studies demonstrating increased mRNA levels for different TGF-β isoforms shortly after outlet obstruction (e. g. 24), and on the documented repression of miR-29 by TGF-β/SMAD3 [11]. [score:1]
Thus we measured the eight validated miR-29 target proteins (the same ones measured after inhibitor transfection) at 6 weeks of obstruction. [score:1]
c-Myc and NF-κB are also known to repress miR-29 [11, 18], and both pathways have previously been shown to be activated in outlet obstruction and by mechanical distension [37- 39]. [score:1]
The proposed mo del fits the data presented in this article, but alternative interpretations are possible and steps upstream of miR-29 repression need in vivo corroboration. [score:1]
SMAD3 activation, which is known to be involved in TGF-β -mediated repression of miR-29, was not significantly increased at 10 days when miR-29b and miR-29c appeared to be maximally repressed. [score:1]
c-Myc, Hdac3 and Ezh2 form a repressive complex that binds to conserved sequences in the miR-29a/b1 and miR-29b2/c promoters [18]. [score:1]
MiR-29 -mediated extracellular matrix remo deling has been demonstrated in the infarcted heart [10] and during aortic aneurysm progression [7- 9], but miR-29 also plays roles in cell proliferation, muscle differentiation and apoptosis [11]. [score:1]
It comprises three miRNAs (miR-29a, miR-29b, and miR-29c) derived from two independent genes [10]. [score:1]
This in turn (2) activates multiple signaling pathways including c-Myc, NF-κB and TGF-β/SMAD3 that in turn repress miR-29. [score:1]
Combined, these findings provide support for our hypothesis that miR-29 reduction contributes to increased protein synthesis in the bladder following outlet obstruction and that this in turn influences matrix properties and stiffness (Figure S2). [score:1]
We hypothesized that miR-29 repression may contribute to increased detrusor stiffness in outlet obstruction. [score:1]
We propose that bladder distension leads to repression of miR-29 via three distinct mechanisms and that this has an impact on tropoelastin and Sparc synthesis and on tissue mechanical properties. [score:1]
To address this hypothesis we examined if SMAD proteins are phosphorylated and whether miR-29 is reduced in outlet obstruction. [score:1]
De-repression of Sparc may thus also contribute to a miR-29 -mediated change of detrusor stiffness in outlet obstruction. [score:1]
In view of this outcome we tested if Eln and Sparc mRNAs were individually correlated with miR-29 in outlet obstruction. [score:1]
Added to the correlation between miR-29c and Col4a1 mRNA this favors a causal relationship between the repression of miR-29 and the increase of Col4a1 in outlet obstruction. [score:1]
The impact of miR-29 in outlet obstruction is likely underestimated by measuring levels of mRNAs because an important mechanism of miRNAs is translational repression. [score:1]
[1 to 20 of 65 sentences]
7
[+] score: 144
Besides, the study also provided evidence to confirm the up-regulation of miR-29a expression in colon may increase the intestinal membrane permeability in IBS rats through the down-regulation of AQPs(AQP1, AQP3, AQP8). [score:9]
Finding out biological function of miRNAs, proved its expression and regulation mechanism eventually, will have profound significance for better understanding of IBS-D. In a word, our findings may lead to new therapeutic targets [34] for the treatment of IBS-D with increased intestinal permeability via miR-29 regulation. [score:7]
Interestingly, compared with IBS-D control group, the expression of the three kinds of AQPs was higher in IBS-D+miR-29a antagomir group, which indicated the deceased of miRNA-29a have an up-regulation on AQPs. [score:5]
On the contrary, while miR-29a antagomir added, the expression increased compared with IBS-D control group, indicating miR-29a regulated the expression of AQPs, which showing negative correlation. [score:5]
The expression of miR-29a, the concentration of the K [+] and Lactate Dehydrogenase(LDH) and the expression of AQPs were detected. [score:5]
Study indicated miR-29a regulated the intestinal permeability target on AQPs. [score:4]
Compared with the control group(1±0.031), the expression of miR-29a increased significantly in IBS-D control group(2.09±0.022), IBS-D +miR-29a NC group(2.047±0.064) and IBS-D+miR-29a antagomir group(1.403±0.042), showing extremely differences(P<0.001), which showed the expression of miR-29a increased in IBS-D rats. [score:4]
Study displayed the up-regulated miRNA-29 resulted in the increased intestinal permeability [24]. [score:4]
Moreover, another research shown that altered miR-29a expression in intestine may regulate intestinal permeability in IBS patients through glutamine dependent mechanisms as proved by the functional interaction between miR-29a and the GLUL [25]. [score:4]
Compared with IBS-D control group(2.09±0.022), the expression of miR-29a decreased significantly in IBS-D+miR-29a antagomir group(1.403±0.042), showing extremely differences (P<0.001), which indicated antagomir blocked out the expression of miR-29a (Figure 2). [score:4]
Moreover, other targets of miR-29a should also be found in IBS-D to complete the mechanism in the future. [score:3]
Zhou [24] found that miR-29 targets on nuclear factor-κB-repressing factor and Claudin 1 to increase intestinal permeability. [score:3]
The above date showed the higher expression of miR-29a lead to the decreased of concentration of K [+] which is a sign of intestinal membrane permeability. [score:3]
Hence, miR-29a influenced the permeability, as the higher expression of miR-29a in the IBS-D control group and IBS-D+miR-29a NC group lead to the higher leakage rates of LDH, showing positive correlation. [score:3]
The change of miR-29a expression in the colonic epithelial cells of IBS-D rats and the effect of miRNA-29a antagomir. [score:3]
Our study proved that diarrhea-predominant IBS rats have increased intestinal permeability which is associated with the increase of miR-29a expression in colon epithelial cells. [score:3]
Thus, we confirmed that the increased expression of miRNA-29a in IBS-D led to the deceased of AQPs, which affected the intestinal permeability. [score:3]
Thus, further studies are needed to demonstrate miR-29a as a treatment target in the IBS-D, and the relationship between AQP1, AQP3, AQP8 and intestinal permeability are supposed to be clarified. [score:3]
In summary, our study is unique that we concentrated on the protein level in IBS-D on the basis of increased expression of miR-29a. [score:3]
Combined former and this studies, we infer that miRNA-29a influences the intestinal membrane permeability through multiple target. [score:3]
Group C: IBS-D rats primary colonic epithelial cells +miR-29a NC(negative control group relative to group D, which hardly influence the expression of miR-29a). [score:3]
Group D: IBS-D rats primary colonic epithelial cells +miR-29a antagomir(antagomir were added to increase the expression of miR-29a). [score:3]
The concentration of K [+] change proved the intestinal membrane permeability inceased significantly with the miR-29a increasing in the IBS-D rats, showing the real function of miR-29a in regulating the intestinal membrane permeability. [score:2]
Compared with IBS-D control group, the expression of AQPs increased significantly in IBS-D+miR-29a antagomir group. [score:2]
Compared with the control group, the expression of AQPs decreased significantly in IBS-D control group, IBS-D +miR-29a NC group. [score:2]
Compared with IBS-D control group, the expression of AQP1 increased significantly in IBS-D+miR-29a antagomir group (P<0.001). [score:2]
Compared with IBS-D control group, the expression of AQP3 increased significantly in IBS-D+miR-29a antagomir group(P<0.001). [score:2]
Our study found that the higher expression of miR-29a resulted in the increasing of intestinal membrane permeability in IBS-D. Interestingly, compared with IBS-D control group, concentration of K [+] decreased significantly while concentration of LDH increased significantly in IBS-D+miR-29a antagomir group. [score:2]
What’s more, the obliteration of miR-29a led to decreased intestinal permeability contrast to the IBS-D control group, manifesting that miR-29a is a critical factor to regulate intestinal permeability. [score:2]
Compared with the control group, the expression of miR-29a increased significantly in IBS-D control group, IBS-D +miR-29a negative control(NC) group, which reflected that miR-29a increased in IBS-D rats. [score:2]
Moreover, miR-29a increased in IBS patients, and researchers conjectured miRNA-29a may effect on intestinal membrane permeability through its regulation of GLUL in IBS [25]. [score:2]
All above reflected that miRNA-29a was a key point to regulation of the intestinal membrane permeability. [score:2]
Compared with IBS-D control group, the expression of miR-29a decreased while miR-29a antagomir added, showing an actual function of obliteration. [score:2]
However, how miR-29a regulates the permeability is only partly known yet. [score:2]
The quantitation of PCR products relatively was conducted by detected the colonic epithelial cells MiR-29a expression changes. [score:2]
Nonetheless, what proteins regulated by miR-29a to affect the intestinal membrane permeability remains unknown. [score:2]
Compared with the control group(0.227±0.014), the expression of AQP8 decreased significantly in IBS-D control group(0.108±0.007), IBS-D+miR-29a NC group(0.101±0.007) and IBS-D+ miR-29a antagomir group(0.194±0.003), showing extremely differences(IBS-D control group and IBS-D+miR-29a NC group P<0.001, IBS-D+ miR-29a antagomir group P<0.05). [score:2]
MiR-29a increased the intestinal membrane permeability of colonic epithelial cells by reducing the AQPs expression in IBS-D rats. [score:2]
Compared with IBS-D control group(, the expression of AQP8 increased significantly in IBS-D+miR-29a antagomir group(P<0.001) (Figure 5). [score:2]
Since IBS-D is the most part in IBS, the goal of our study was to evaluate the expression of miRNA-29a in colonic epithelial cells in IBS-D rats and clarify the mechanism of miRNA-29a regulating the intestinal membrane permeability by AQP1, AQP3, AQP8. [score:2]
Also, the function of miR-29a in regulating the intestinal membrane permeability was confirmed. [score:2]
Compared with the control group(0.229±0.013), the expression of AQP1 decreased significantly in IBS-D control group(0.132±0.010), IBS-D +miR-29a NC group(0.124±0.010) and IBS-D+ miR-29a antagomir group(0.197±0.005), showing extremely differences(IBS-D control group, IBS-D+miR-29a NC group (P<0.001), IBS-D+ miR-29a antagomir group P<0.05). [score:2]
Compared with the control group(0.221±0.004), the expression of AQP3 decreased significantly in IBS-D control group(0.111±0.005), IBS-D +miR-29a NC group(0.102±0.008) and IBS-D+ miR-29a antagomir group(0.182±0.011), showing extremely differences(IBS-D control group and IBS-D+miR-29a NC group P<0.001, IBS-D+ miR-29a antagomir group P<0.01). [score:2]
Our goal was to evaluate the expression change of microRNA-29a(miR-29a) in colonic epithelial cells in IBS rats and clarify the mechanism of miR-29a increasing the intestinal membrane permeability through aquaporins(AQPs). [score:1]
All in all, the former studies indicated miR-29a has significant effect on intestinal membrane permeability. [score:1]
MiRNA-29a regulated AQP1, AQP3, AQP8 in the colonic epithelial cells of IBS-D. DISCUSSION. [score:1]
The expression of AQP1, AQP3 and AQP8 decreased in IBS-D control group(0.132±0.010,0.110±0.005,0.108±0.007) compared with the control group (P<0.001) while it increased in IBS-D+miR-29a antagomir group(0.197±0.005,0.182±0.011,0.194±0.003) compared with IBS-D control group(P<0.001). [score:1]
MiRNA-29a is a member of miRNA-29 family. [score:1]
MiRNA-29a regulated concentration of K [+] in the colonic epithelial cells of IBS-D. The concentration of LDH. [score:1]
In order to explain how miR-29a influences intestinal membrane permeability through potential mechanistic pathways, we focus on AQPs. [score:1]
MiRNA-29a regulated concentration of LDH in the colonic epithelial cells of IBS-D. Western blot. [score:1]
The miR-29a expression increased in IBS-D control group(2.090±0.022) compared with the control group(1.00±0.031) (P<0.001) while it decreased in IBS-D+miR-29a antagomir group(1.403±0.042) compared with IBS-D control group(P<0.001). [score:1]
D: IBS-D + miR-29a antagomir. [score:1]
Besides, the miR-29a NC was confirmed to be a great negative control in related to miR-29a antagomir. [score:1]
MiR-29a has been confirmed to take part in the regulation of intestinal membrane permeability in IBS. [score:1]
C: IBS-D +miR-29a NC. [score:1]
The IBS-D+miR-29a negative control(NC) group, a comparison with IBS-D+miR-29a antagomir group, each date showed the similar trend to the IBS-D control group. [score:1]
We firstly found the relation between miR-29a and AQPs in the IBS-D colon tissues. [score:1]
[1 to 20 of 58 sentences]
8
[+] score: 130
MiR-1 targets both DnaJ-B1& Nucleolin; miR-23a target nucleolin & SMAD4 and miR-29a targets DnaJ-B1 & SMAD4 3′UTR. [score:7]
MicroRNA anti-sense inhibitors (miR-29a and miR-23a) down-regulate the glucose transport activity in insulin-added condition in L6 cell-line. [score:6]
The miR-1 and miR-29a target DnaJ-B1 whereas nucleolin is targeted by miR-23 and miR-1 with a statistical significance (Fig. 12, I&II). [score:5]
This target protein SMAD4, whose 3′UTR contains the binding sites for miR-29a, let7a and miR-1 that are over-expressed in the IPGR male sk. [score:5]
I asked the question directly in an established rat cell-line whether miR-1, miR-23a or miR-29a play a role in regulating glucose transport activity (GTA) in vitro, delineating the possible functional correlation of these microRNA(s) over-expressed in SMSP muscle tissues. [score:5]
Although LNA based-miRCURY microarray produced results reproducible in further analyzing differences in in vitro confirmation of the over -expression of let7a, miR1, miR-29a and miR-23a in SMSP samples, the approach taken here was focused on the identification of target protein genes for the respective microRNAs that affect the glucose transport pathways in SKM. [score:5]
The over -expression of miR-29 in 3T3-L1 adipocytes inhibited insulin-stimulated glucose uptake [37]. [score:5]
Fig. 13(II) shows the exogenous miR-29a does not alter the vector luciferase expression upon transfection, but represses significantly (p = 0.02) the SMAD4 3′UTR mediated luciferase expression. [score:5]
The protein factors SMAD4, DnaJ-B1, and nucleolin, are possible targets of miR-29a, miR-23a and miR-1. Cellular fractionation of possible target proteins: Nuclear fraction. [score:5]
This suggested that excess miR-29a molecules might have targeted multiple targets, giving rise to functional stimulation of GTA whereas; the endogenous depletion caused unchanged GTA in absence of insulin. [score:5]
So, miR-29a and miR-23a may directly or indirectly affect SMAD4 expression. [score:5]
In adipocyte cell-line 3T3-L1, it has been shown by Aibin H et al. [64] that miR-29a/b/c over -expressions through Adenovirus -mediated delivery were accompanied by the inhibition of insulin -dependent glucose transport activity. [score:5]
The miR-29 group of microRNAs was found to be up-regulated in muscle and fat tissues of Goto–Kakizaki rats, a non-obese rat mo del of diabetes mellitus (T2DM). [score:4]
MiR-29a significantly up-regulates GTA (p<0.01), whereas both miR-1 and miR-23 tend to increase the transport activity (for miR-1 p = 0.06 and 0.08; for miR-23a p = 0.08 and no difference; Fig. 9A, B) compare to the mock treatment. [score:4]
The miR-23a and miR-29a transfections led to the 50% down-regulation of SMAD4 level in L6 cells although there was no miR-23a recognition site for the SMAD4 3′UTR (Fig. 8, 12, I&II). [score:4]
MiR-29a and miR-23a target SMAD4 to regulate glucose transport in rat skeletal muscle. [score:4]
Mimic microRNAs miR-29a and miR-23 up-regulate the glucose transport activities in L6 SKM cell-line as insulin-independent and dependent manner respectively. [score:4]
SMAD4, is one of the targets for miR-29a and/or miR-23a: Bioinformatics analysis. [score:3]
So, considering the gain of function experiment using Pre-miR-29a, it is very likely that the microRNA concentration is critical in targeting multiple factors to affect insulin-independent glucose transport activity. [score:3]
Only two-fold or nearly two-fold over -expression has been observed in some cases, mostly in miR-29a for SMSP and miR-129* for CMCP. [score:3]
The inhibition of TGF-β by imatinib restores the level of miR-29a in fibroblast cells [69]. [score:3]
The over -expression of miR-29a, 23b, 23a, 1 and let7a in SMSP (1–6):Hy5 and miR-129*, 103, 483, 107 and 326 in CMCP (1–6):Hy3 have been observed. [score:3]
Distinctively, miR-1, let7a and miR-29a expressions were much higher in SMSP experimental samples (n = 6) than in control CMCP rat muscles. [score:3]
SMAD4 is one of the targets for miR-29a and/or miR-23a: Analysis in Cell-line. [score:3]
According to the alignment scores and energy levels, let7a>miR-29a>miR-1 towards SMAD4 target sites (Fig. 8). [score:3]
The 3′UTR of these mRNAs harbor the miRNA target sites (DnaJ1 contains miR-29a and Nucleolin (C23) contains miR-1 sites) and this data is supported by the transfections of Pre-miR(s) in L6 myoblast cells (Fig. 12). [score:3]
Another regulatory protein dnaJ-B1, an isoform of HSP40 chaperone, has the binding site for miR-29a of alignment score 147 and stability −19.55 (Fig. 8). [score:2]
The miR-29a is proven to be the real candidate to interact with the SMAD4 3′UTR and also regulate the glucose transport activity in L6 cells. [score:2]
Anti-miR-29a also showed a significant decrease in GTA (p<0.05), indicating a role for the regulation in glucose transport process in SKM. [score:2]
Groups of tissue-specific (e. g., miR-1, miR-206, miR-208) and non-tissue-specific (e. g., miR-29a, miR-23a) microRNAs have been found to control skeletal muscle development in growth and differentiation [13]– [19]. [score:2]
The miR-29a and miR-23a are two such micro -RNAs identified that modulate the glucose transport pathway in vitro as a general and insulin -dependent manner. [score:1]
Given the specificity of the LNA -based anti-miR(s), it is not conceivable to imagine that anti-miR-29a would react with other related miR(s) to make the GTA unchanged under the condition of insulin-independent manner. [score:1]
0034596.g008 Figure 8 miR-1, miR-29a and miR-23a for SMAD4, DnaJ-B1 and nucleolin 3′UTRs. [score:1]
But the functional significance of miR-29a, in the absence of insulin, could not be verified under the condition. [score:1]
The 3′UTR of SMAD4 harbor the recognition sites for miR-1, miR-29a and let-7a according to the bioinformatics analysis (Sloan-Kettering Institute micro -RNA site, http://www. [score:1]
Transient transfections of precursor micro -RNA(s) and anti-miR(s) in rat L6 skeletal muscle cell-line demonstrate a stimulatory role for miR-29a in glucose transport activity in general whereas miR-23a for insulin -dependent function in the same. [score:1]
In another paper, TGF-β reduced the level of miR-29a and vice versa. [score:1]
DnaJ B1 and nucleolin 3′UTR recognizes miR-29a and miR-1 respectively with very strong affinities (Fig. 8) according to miRANDA alignment score and energy of stabilizations. [score:1]
Precursor microRNA mimics- Mimics of endogenous precursor micro -RNA synthetic molecule for rat, namely, Pre-miR-1, Pre-miR-23a, Pre-miR-23b and Pre-miR-29a were purchased from Ambion Inc. [score:1]
Central co-SMAD, Mothers Against Decapentaplegic Homolog 4, bears putative binding sites for three different microRNAs miR-1, miR-29a and let7a (Fig. 8). [score:1]
miR-1, miR-29a and miR-23a for SMAD4, DnaJ-B1 and nucleolin 3′UTRs. [score:1]
The miR-29a recapitulates the in vivo data where there is a drastic diminution of SMAD4 level in rat experimental tissues. [score:1]
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9
[+] score: 110
As extracellular or cytoskeletal molecules are thought to be important in maintaining normal development, and their abnormal expression may cause pathogenesis, we chose Tm1α and 2β molecules, predicted targets of the miR29 family and used Western blot analysis to examine their protein expression in cell extracts isolated from LECs transfected with miR29a or 29c inhibitors (Fig. 4). [score:10]
As shown in Figure 6A and B, when the luciferase gene carried 3′ UTR region of TM1α's transcript, the luciferase activity was inhibited by overexpressing miR29c compared with the negative control, but was not significantly inhibited by overexpressing miR29a (Fig. 6A). [score:8]
These data suggest that down-regulation of let7c, miR29a and miR29c, and miR126 may be a major event during cataract formation in the SCR, as changes in miRNA expression levels were increased in cataractous lenses. [score:6]
Relative expression of miRNAs let7b, let7c, miR-29a, miR29c and miR126, which are significantly up- or down-regulated during the progression of lens development, were measured following RNA extraction using RT-PCR. [score:5]
These results suggest that Tm1α expression may be directly regulated by miR29c, not miR29a. [score:5]
Fig. 4Elevated expression of Tm1α/2β proteins in lens epithelial cells (LECs) transfected with miR29a and 29c inhibitors. [score:5]
Rat TM1α3′-UTR, rat TM2β 3′-UTR was cotransfected with miExpress™ Precursor miRNA Expression Clone for rno-miR29a mimic or rno-miR29c mimics in pEZX-MR04 vector with eGFP reporter gene, Precursor miRNA scrambled control for pEZX-MR04 or empty pEZX-MR04 vector purchased from GeneCopoeia Inc. [score:5]
For inhibition of miRNAs, miRIDIAN Hairpin inhibitor (Thermo scientific, Lafayette, CO, USA), Rat rno-miR29a and 29c were used and transfected into SCRs with cataract and SCRs without cataract LECs. [score:5]
Effect of miR29a and 29c inhibitors on the expression of Tm1α/2β levels. [score:5]
Effect of miR29a, 29c and let7b overexpression on the expression of Tm1α/2β proteins. [score:5]
To further determine whether miR29a or miR29c regulates Tm1α/2β expression, we transfected LECs isolated from cataractous SCRs with precursors (pre) of these miRNAs. [score:4]
Interestingly, RT-PCR assessment of level of miRNAs in cataractous lenses showed that four miRNAs–let7c, miR29a and 29c, and miR-126–were significantly down-regulated, suggesting a plausible contribution by these miRNAs to cataractogenesis (Fig. 3). [score:4]
On the other hand, when the luciferase gene carried 3′ UTR region of TM2β's transcript, the luciferase activity was not significantly inhibited by overexpressing miR29a and miR29c compared with the negative control (Fig. 6B). [score:4]
Relative expression levels of miRNAs, let-7b, let-7c, miR-29a, miR-29c, miR-204, miR-126, miR-451 in ED16, 4W and 14W lenses are represented as histograms with normalized averages ± SD. [score:3]
Our study revealed that Tm 1α and 2β are putative target genes for miR29a or 29c. [score:3]
However, let7c, miR-29a, miR29c and miR126 were significantly down-regulated in SCR with cataract lenses compared with SCR without cataract lenses at both ages 7 and 21 weeks. [score:3]
Immunoblotting experiments revealed greater abundance of Tm1α/2β protein in LECs transfected with miR29a and 29c inhibitor. [score:3]
Cells were overexpressed with let7b, miR29a and miR29c by transfecting them with miRNA precursors. [score:3]
2XUp  let-7b poly (ADP-ribose) polymerase family, member 3, Glutaredoxin-2, Fibroblast growth factor 20 (FGF-20), FGF -binding protein 1, Multiple EGF-like domains 6 precursor, Hsp70 -binding protein 1, IGF2 mRNA -binding protein 3, Myc proto-oncogene protein (c-Myc), Hsp70 -binding protein 1 (HspBP1), FGF receptor activating protein 1, Tumor protein p53-inducible nuclear protein 1, Vimentin, Thioredoxin mitochondrial precursor (Mt-Trx)  let-7c poly (ADP-ribose) polymerase family, member 3, Vascular endothelial growth factor C precursor (VEGF-C), FGF-20, IGF2 mRNA -binding protein 3, Glutaredoxin-2, NF-kappa-B essential modulator (NEMO) (NF-kappa-B essential modifier), Hsp70 -binding protein 1, c-Myc, Heat shock factor 2-bindlng protein, AQP-2, Tumor protein p53-inducible nuclear protein 1, Vimentin, Mt-Trx  miR-29a Tropomyosin alpha-1 chain (Tropomyosin-1) (Alpha-tropomyosin), glutathione peroxidase 7, PDGF B-chain, Dicer1  miR-29c Tropomyosin-1, Dicer1, TGF-beta-2, glutathione peroxidase 7, PDGF A-chain, Multiple EGF-like domains 6 precursor, FGF receptor–activating protein 1, SMAD 6, AQP-11  miR-204* Tropomyosin-1, Hsp70 -binding protein 1, Mitogen-activated protein kinase 4, Gamma crystallin D, IGFBP-1, Glutathione S-transferase P (GST class-pi), Sulfiredoxin 1 To predict genes targeted by miRNAs, Sanger miBase Software was utilized. [score:3]
Data revealed that let7c, miR29a and miR29c were significantly up-regulated in 21W lenses compared with 7W SCR without cataract (Cat−) or SCR with cataract (Cat+). [score:3]
Figure 5 shows the expression levels of Tm1α/2β proteins in LECs transfected with miR29a and miR29c precursors isolated from SCR with cataract. [score:3]
The increased expression of these molecules was inversely related to miR29 in LECs of SCRs with cataract. [score:3]
Fig. 5 Lens epithelial cells (LECs) from Shumiya Cataract Rats (SCR) with cataract transfected with let7b, miR29a and 29c precursors display reduced expression of Tm1α/2β proteins. [score:3]
As shown in Figure 3, Let 7c, miR-29a and miR29c were up-regulated in non-cataractous LECs/lenses compared with cataractous. [score:3]
In parallel experiments, we used miR29a inhibitor, and found it ineffective compared with miR29c. [score:2]
Levels of let-7b, let-7c, miR-29a, miR-29c and miR-204 were dramatically altered during the progression of development. [score:2]
The seven miRNAs (let7b, 7c, miR29a, miR-29c, miR204, miR126, miR51) listed in Table 3 were used for validation experiments. [score:1]
Mouse lens epithelial cells were cotransfected with rat TM1α (A) or rat TM2β (B) with rno-miR29a mimic, rno-miR29c mimics in pEZX-MR04 vector with eGFP reporter gene, precursor miRNA scrambled control for pEZX-MR04 or empty pEZX-MR04 vector. [score:1]
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10
[+] score: 102
Although there are presumably additional targets regulated by miR-29 and miR-203, our experiments suggest that VEGFA suppression is mediated, at least in part, by overexpression of these miRNAs. [score:8]
Our results confirmed that VEGFA is a direct target of these miRNAs, as both miR-29a,c and miR-203 strongly and specifically suppressed endogenous VEGFA expression in vitro. [score:8]
Relative expression levels of miR-29 family members (A) and miR-203 (B) in isolated (ISO) rats are in comparison to control levels expressed as 1 on the graph. [score:5]
These data suggest that overexpression of miR-29 and miR-203 contributes to isolation -induced delays of wound healing, partially by suppressing VEGFA. [score:5]
0072359.g004 Figure 4(A) The predicted miR-203 and miR-29 targeting sequences located in the 3’-untranslated region (3’-UTR) of VEGFA mRNA. [score:5]
Cells were co -transfected with constructs containing the predicted targeting sequence (WT) or mutated targeting sequence (Mutant) cloned into the 3’-UTR of the reporter gene, along with miRNA mimics of miR-29 or miR-203. [score:5]
Based on bioinformatics analysis, a highly conserved miR-29 isoform -targeting sequence and a miR-203 -targeting sequence were identified in the VEGFA mRNA 3’ UTR (Figure 4A). [score:5]
miR-29a, miR-29c (Figure 4B) and miR-203 (Figure 4C) significantly reduced activity of firefly luciferase by directly targeting the rat VEGFA 3′ UTR. [score:4]
MiR-203 and miR-29 directly target VEGFA mRNA. [score:4]
Wound closure was assessed daily and tissues were collected for determination of gene expression levels and miRNAs (i. e., miR-29a,b,c and miR-203). [score:3]
As shown in Figure 4D, ectopic transfection of miR-29a, miR-29c and miR-203 in HEK293 cells led to a significant decrease in VEGFA protein expression. [score:3]
miR-29a,c and miR-203 Suppress Endogenous VEGFA. [score:3]
Expression of miR-29 family members, miR-203 and SOCS3 mRNA in wounded tissues by qRT-PCR. [score:3]
In this study, VEGFA was the only healing -associated mRNA targeted by miR-29 and miR-203 (out of the nine that were tested). [score:3]
0072359.g003 Figure 3 Expression of miR-29 family members, miR-203 and SOCS3 mRNA in wounded tissues by. [score:3]
In accordance with these findings, our results demonstrate that miR-29 family members and miR-203 were persistently overexpressed across healing in isolated rats. [score:3]
miR-29a,c and miR-203 Target VEGFA. [score:3]
For functional analysis, miR-29 (a, b, c) mimics, miR-203 mimics and non -targeting miRNA mimics (Dharmacon, Lafayette, CO, USA) were transfected into cells using DharmaFECT Transfection Reagent 1 (Dharmacon) per the manufacturer’s instructions. [score:3]
Reduced expression of miR-29 family members was recently reported in different fibrotic organs [31- 33]. [score:3]
Interestingly, in this study, we identified a negative correlation between levels of VEGFA and the expression of miR-29a,c and miR-203 in wounds. [score:3]
MiR-29 is a typical multifunctional miRNA which is involved in regulating the epithelial-mesenchymal transition, cellular differentiation, extracellular matrix remo deling, and angiogenesis [29, 30]. [score:2]
Mutation of the putative miR-203 binding site abolished the effect of miR-203 while leaving the action of all three miR-29 isoforms unaffected (B). [score:2]
Similarly, mutation of the putative miR-29 site led to abolishing the action of the miR-29 isoforms (Figure 4C). [score:2]
Intriguingly, both miR-29 and miR-203 are important regulators of wound-specific cell functions and the cytokine network [38, 39]. [score:2]
Similarly, mutation of the putative miR-29 binding site abolished the action of the miR-29 isoforms (C). [score:2]
As expected, mutation of the putative miR-203 binding site abolished the effect of miR-203 while leaving the action of all three miR-29 isoforms unaffected (Figure 4B). [score:2]
In this study, we hypothesized that social isolation delays oral mucosal wound healing, and healing -associated genes and miRNAs (i. e., miR-29 and miR-203) play a role in this process. [score:1]
Both miR-29a and miR-203 reduced luciferase activity by ≥ 40% (p<0.001) (Figure 4B, C). [score:1]
Isolation Stress and Levels of miR-29 and miR-203. [score:1]
Considering the important role of miR-29 and miR-203 in both dermal and mucosal repair, these results suggest a putative mechanism for isolation -induced healing impairments through the modulation of VEGFA. [score:1]
This suggests there are novel roles of miR-29 and miR-203 in isolation-impaired healing. [score:1]
Intriguingly, the isolated rats persistently exhibited higher levels of miR-29 family members and miR-203. [score:1]
To test this, we selected and determined the levels of two miRNAs in wounds: miR-29 and miR-203. [score:1]
In both the putative miR-29 and miR-203 binding sites, the 6 to 8 nucleotides of the “seed region” were replaced with a restriction enzyme site with minimal complementarity to the miRNA sequence (see Materials and). [score:1]
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[+] score: 59
MicroRNA-29a and 29b-1 are processed from chromosome 7, and miR-29b-2 and 29c are transcribed from chromosome 1. Since forced overexpression of miR-29 markedly suppresses collagen 1 A1 mRNA and protein expression [16, 17], miR-29 plays an anti-fibrotic role in the liver and other organs [18]. [score:7]
Next, we examined exosomal miRNA expression in other animal mo dels of gastrointestinal disease to determine whether increased expression of exosomal miR-29a-3p was specific to chronic reflux esophagitis. [score:7]
In conclusion, our results demonstrated that exosomal miR-29a-3p might assist in the diagnosis of GERD, and increased expression of esophageal miR-223-3p was inversely associated with expression of E2F1 or STAT3 in esophageal tissue reflux esophagitis. [score:5]
Precise mechanisms of increased expression of exosomal miR-29a-3p in chronic reflux esophagitis, as well as the discrepancy of miR-29a-3p expression between serum exosomes and esophageal tissue, are unknown. [score:5]
The expression levels of these miRNA and mRNA are presented as ratios to the mean value in control tissue on day 3. The expression levels of miR-29a-3p and miR-128-3p in reflux esophagitis were significantly lower than those of the controls on day 3 (Figure 4A,B). [score:5]
However, the reason why exosomal miR-29a-3p was downregulated in the acute phase was not clear. [score:4]
The expression levels of these miRNA are presented as ratios to the mean value in exosomal miRNA of the control on day 3. The expression level of exosomal miR-29a-3p in reflux esophagitis was significantly lower on day 3, but significantly higher (2.4-fold) on day 21 compared with controls (Figure 2A). [score:4]
The expression patterns of miR-29a-3p, miR-128-3p and miR-3473 were not dramatically changed during acute to chronic phases (Figure 4A,B,D). [score:3]
The relative expression level of exosomal miR-29a-3p was presented as ratios to the mean value of the control in each mo del (Figure 3). [score:3]
Microarray analysis revealed an upregulation of miR-29a-3p, miR-128-3p, miR-223-3p and miR-3473 in reflux esophagitis (p < 0.05 compared to controls). [score:3]
These results revealed that only miR-29a-3p expression significantly increased in the chronic phase of reflux esophagitis, suggesting exosomal miR-29a-3p might be a novel candidate surrogate marker for chronic reflux esophagitis. [score:3]
The expression of exosomal miR-29a-3p in the acute phase of reflux esophagitis, gastric ulcer and colitis was significantly lower compared with the control. [score:2]
Increased expression level of exosomal miR-29a-3p was specific to chronic reflux esophagitis compared with gastric ulcers and dextran sulfate sodium (DSS)-colitis mo dels. [score:2]
Increases in serum exosomal miR-29a-3p were specific to chronic reflux esophagitis since exosomal miR-29a-3p was not increased in other gastrointestinal mucosal injury mo dels, including gastric ulcers and colitis. [score:1]
The miR-29 group is composed of miR-29a, 29b-1, 29b-2, and 29c. [score:1]
These results suggest that serum exosomal miR-29a-3p might be a specific marker for GERD. [score:1]
First, we found that only the exosomal miR-29a-3p level was significantly increased in chronic reflux esophagitis among four miRNAs identified by microarray analysis. [score:1]
However, our results showed that fibrosis was not observed and esophageal miR-29a-3p did not increase in the chronic phase of reflux esophagitis. [score:1]
The Specificity of Exosomal miR-29a-3p with Reflux Esophagitis. [score:1]
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12
[+] score: 58
Interestingly, ZL-F had higher cardiac Med13 expression than ZL-M. (d– f) Graphs show qRT-PCR data on the expression of cardiac microRNA miR-29a, b and c. Expression of all miR-29 family miRNAs were increased in ZDF-F and ZDF-M. miR-29c was the most differentially expressed miRNA between male rats (f) whereas miR-29b was the most differentially expressed miRNA between female rats (e). [score:11]
Since increased expression of miR-208a is associated with cardiac hypertrophy, the female-specific increase in cardiac miR-208a expression could have contributed to the increased susceptibility to cardiac hypertrophy in ZDF-F. Increases in the circulating levels of miR-29 family miRNAs in children with T1DM and adults with T2DM 42, 43 emphasize the clinical relevance of this biomarker in DM. [score:5]
Differential expression of miR-29b was highest between ZDF-F and ZL-F, while differential expression of cardiac miR-29a and c were prominent between ZDF-M and ZL-M. Collectively our data show that T2DM -associated CVD progression in ZDF-F and ZDF-M is structurally and mechanistically different. [score:5]
DM -associated dysregulation of miR-208a-MED13 signaling and increase in miR-29 family miRNAs occur in both male and female ZDF rats, however, only ZDF-F rats exhibited myocardial damage indicating that cardiac repair is impaired in ZDF-F. It is conceivable that the higher expression of cardio-reparative Agtr2 in ZL-F compared to ZL-M (Fig.   9a) could have provided increased protection despite the higher expression of pro-hypertrophic miR-208a in ZL-F heart compared to ZL-M heart. [score:4]
Here we show for the first time that while all miR-29 family miRNAs increased in response to diabetes in both sexes, there was a sex difference in their expression patterns. [score:3]
Thus, increases in the expression levels of the individual DM -associated miR-29 isoforms are also largely dependent on sex. [score:3]
TaqMan MicroRNA Assays (Life Technologies) primers for miR-208a, miR-29a, b, c, and U6 snRNA were used for miRNA targets, and Med13 and 18 S rRNA for mRNA targets. [score:3]
Cardiac miR-29 family miRNA expression patterns are different in male and female diabetic rats. [score:3]
Thus, there were sex differences in miR-29 family miRNA expression. [score:3]
Cardiac expression of AT2R (Agtr2), Med13, miR-208a, and miR-29 family miRNAs were determined using mRNA and miRNA isolated from frozen heart tissues as described previously [44]. [score:3]
Figure 9Expression patterns of cardioprotective Agtr2 and Med13, and cardio- deleterious miR-208a and diabetic marker miR-29 family miRNAs in heart tissues of 5-month old healthy and diabetic, male and female rats. [score:3]
Med13 (MED13)Prevents weight gain, improves insulin sensitivity and cardiac function 36, 37. miR-208aSuppresses Med13, and promotes cardiac hypertrophy 38, 39. miR-29a, b, & cBlood -based biomarker for T1DM and T2DM and promotes cardiac disarray 40– 42, 64– 66 We reported recently that there are significant differences in cardiac cytokine proteins between healthy and diabetic male rats [21]. [score:3]
Given the critical role of miR-29 in both DM and cardiac structure, we compared the cardiac expression of miR-29a, b and c between our groups. [score:2]
Cardiac expression of all members of the miR-29 family increased in both ZDF-F and ZDF-M compared to ZL-F and ZL-M (Fig.   9d–f, p < 0.05). [score:2]
miR-29a is a blood biomarker in humans for hypertrophic cardiomyopathy and fibrosis [67]. [score:1]
Members of the microRNA miR-29 family (miR-29a, b, and c) serve as mechanistic biomarkers for diabetes (T1DM and T2DM) and cardiovascular damage. [score:1]
We previously showed that increased miR-29 family miRNAs correlate with DM -induced cardiomyocyte disorganization [44]. [score:1]
We showed that elevated miR-29 family miRNAs correlate with increased cardiomyocyte disarray in 15-week old ZDF-M [44]. [score:1]
Diabetes -induced increases in the levels of cardiac miR-29a and 29c were dependent upon the sex of the animal (Fig.   9d and f). [score:1]
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13
[+] score: 58
We have 1) Determined the miRNA profile of perinatal pancreas, which is undergoing large structural and metabolic changes in the period around birth and identified and validated 7 miRNAs regulated more than 1.5-fold from E20 to P2; 2) Localized regulated miRNAs by ISH; 3) Performed focused pathway analysis of pathways affected by regulated miRNAs using predicted mRNA target genes also regulated in perinatal pancreas; 4) Shown that biochemical pathways relating to sterol and lipid biosynthesis and metabolism are affected by the perinatally regulated miRNAs; 5) Validated Srebf1 as target gene of miR-21 and shown an effect of miR-21 and miR-29a on INS-1E beta-cell cholesterol levels. [score:10]
MiR-29 family members are often down-regulated in cancer and forced expression of miR-29a is reported to reduce proliferation and invasiveness presumably via CDC42 and p85alpha dependent up-regulation of p53 [36], [37]. [score:9]
It is possible that up-regulation of miR-21 and/or miR-29a in perinatal rat pancreas act through down-regulation of Srebf1 and other genes in the cholesterol synthesis pathway to fine-tune cholesterol levels and promote functional maturation of beta-cells following birth. [score:7]
Here, miR-29a was expressed in exocrine and endocrine pancreas with highest expression in islets, in line with findings from adult pancreas [12]. [score:5]
E. Total cholesterol levels of INS-1E cells following knock-down of miR-21 and/or miR-29a in INS-1E cells (LNA-21: Knock-down of miR-21, LNA-29a: Knock-down of miR-29a, LNA-scr: Scrambled control LNA, Untransf: Untransfected). [score:4]
To determine whether the presence of multiple targets of miR-21 and miR-29a (Fig. 4) along the cholesterol synthesis pathway resulted in a cumulative effect on cholesterol levels, we extracted and measured cholesterol in INS-1E cells nucleofected with oligonucleotide inhibitors of miR-21 and miR-29a (LNA-21 and LNA-29a) and negative control oligonucleotide (LNA-scr). [score:3]
Thus, inhibition of miR-21 and miR-29a simultaneously and miR-29a by itself increased total cholesterol levels, showing that the increase of miR-21 and miR-29a following birth is likely to functionally participate in the decrease of the cholesterol synthesis pathway. [score:3]
It seems likely that these small effects are functional given that we can increase cholesterol levels by inhibiting miR-21 and miR-29a. [score:3]
4·10 [6] cells were nucleofected with miR-21 and/or miR-29a LNA knock-down, or scrambled LNA oligonucleotide (Exiqon) using an Amaxa nucleofector (Lonza, Copenhagen, Denmark). [score:2]
Whether the perinatal regulation of miR-21 and miR-29a is present in other tissues remain to be investigated; however, cholesterol synthesis of rat liver, intestines and brain decrease sharply at the day of birth and synthesis rates then increase again on postnatal day 2 [47], which is consistent with the mRNA and miRNA expression pattern observed in pancreas. [score:2]
Cells with inhibited miR-29a alone or with miR-21 had increased total cholesterol levels compared with LNA-scr (Fig. 6E, ‘LNA-scr’ vs. [score:2]
MiR-29a was expressed in acinar and islet cells at E20 and changed to being mostly endocrine at P0 and P2. [score:2]
Cluster I and II consisted of miR-29a and miR-21, and miR-125b-5p and miR-23a, respectively, and showed an increased expression at P0 and P2 compared to E20. [score:2]
Localization of miR-21 and miR-29a in perintal rat pancreas at E20, P0 and P2 by in situ hybridization. [score:1]
However, miR-21 and miR-29a were 2.5- and 4-fold increased. [score:1]
MiR-29a has previously been recognized as a miRNA increased in adipose tissue and skeletal muscle in diabetes [34], [35]. [score:1]
The miR-21 binding site of Srebf1 is rat specific; however the human SREBF1 gene contains a binding site for miR-29a, and this miRNA is also increased in islets at P0 and P2 and has an effect on cholesterol levels. [score:1]
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[+] score: 55
Other miRNAs from this paper: rno-mir-144
To further confirm whether the differential expression of PLA2G4A was directly induced by American ginseng, we performed qRT-PCR analysis to determine whether American ginseng affected the expression of miR-144 and miR-29a, both of which can suppress PLA2G4A expression. [score:10]
The expression of miR-144 and miR-29a has been shown to suppress PLA2G4A transcription or translation or to cut the mRNA so that it is targeted for degradation. [score:9]
Our results suggested that PLA2G4A downregulation might be secondary to the upregulation of miR-144 and miR-29a induced by American ginseng treatment. [score:7]
Indeed, Yao et al. previously showed that miR-29a expression was significantly suppressed in FSH -treated cultured rat granulosa cells [40]. [score:5]
This inverse correlation might verify our current results, indicating that upregulated miR-29a and miR-144 induced by American ginseng treatment may play a significant role in protecting ovarian function by regulating the response to hormone stimulation and preventing ovarian aging. [score:5]
However, it is also possible that American ginseng may regulate miR-144 and miR-29a expression to specifically restore PLA2G4A levels. [score:4]
In this study, we used the same treatment regimens and found that American ginseng significantly reduced PLA2G4A expression and increased miR-144 and miR-29a expression in POF ovarian tissues compared to POF induction alone. [score:4]
Additionally, the upstream miRNAs miR-29a and miR-144 were downregulated compared to the POF mo del (P < 0.05, Figure 1(a)). [score:3]
In our previous study, we demonstrated that miR-29a and miR-144 expression decreased in POF ovarian tissues. [score:3]
In our previous study, we also demonstrated that miR-29a and miR-144 expression decreased in POF ovarian tissues. [score:3]
The changes in the PLA2G4A and miR-29a and miR-144 genes suggest that American ginseng exerts its effect by regulating prostaglandin biosynthesis, ovulation, and preventing ovarian aging. [score:2]
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[+] score: 51
As depicted in Fig 8, miR-1, miR-29a, miR-106b and miR-200a was selectively inhibited by H [2]0 [2] treated Pitx2 -overexpressing cells but up-regulated in H [2]0 [2] treated Pitx2 silenced cells at both time points (12h and 24h). [score:8]
HL-1 atrial cardiomyocytes transfected with miR-29 and miR-200 (Fig 8) significantly down-regulate Cacna1c, Hnc4 and Ryr2 expression, while Camk2a was significantly decreased with miR-200 but not miR-29 (Fig 8). [score:6]
Observe that miR-29 and miR-200 over -expression leads to significant decreased of Cacna1c, Hcn4, Ryr2 and Camk2a (except for miR-29a) expression. [score:5]
miR-29 over -expression in HL1 atrial cardiomyocyte deregulate Cacna1c, Hnc4 and Ryr2, influencing therefore both the calcium handling and pacemaker activity, whereas miR-200 regulated Cacna1c, Ryr2 and Camk2a, in addition to Scn5a as previously reported [64], impacting therefore also in calcium handling. [score:5]
qPCR of left atrial chambers demonstrated that miR-1, miR-26b, miR-29a, miR-30e, miR-106b, miR-133 and miR-200 are up-regulated in HTD rats as compared to controls (Fig 1), demonstrating a similar microRNA expression profile as in atrial-specific Pitx2 deficient mice [14, 16]. [score:5]
We provide herein evidences that miR-29 and miR-200 over -expression also contributes to ion channel expression remo deling. [score:5]
Thus these data demonstrate that miR-29 and miR-200 impaired expression also contributes to develop pro-arrhythmogenic substrates. [score:3]
We have previously demonstrated that Pitx2 modulates expression of miR-29 and miR-200, among other microRNAs [16] and furthermore we have demonstrated in this study that modulation of distinct ion channel is greatly influenced by H [2]0 [2] administration while microRNA signature is mostly dependent on Pitx2c but not H [2]0 [2] administration. [score:3]
0188473.g008 Fig 8Analyses of Scn5a, Kcnj2 and Cacna1c (A), miR-1, miR-29a, miR-106b and miR-200b (B) expression in Pitx2 gain and loss-of-function experiments after H [2]0 [2] administration for 12h and 24h, respectively. [score:3]
Whereas it is wi dely documented that redox signaling can compromise ion channel functioning and calcium homeostasis in cardiomyocytes [67], in our system we observed no influence of H [2]O [2] administration on the regulatory impact of Pitx2 in distinct ion channels such as Scn5a, Kcnj2 and Cacna1c as well as multiple Pitx2-regulated microRNAs such as miR-1, miR-26, miR-29 and miR-200, in which redox impairment impact is less documented [68]. [score:3]
miR-29a and miR-200 expression in HL-1 atrial cardiomyocytes transfected cells. [score:3]
Importantly, miR-29 and miR-200 are not significantly impaired in SHR atrial chambers, suggesting that Wnt-microRNA might be a pivotal candidate establishing fundamental differences between HTD and HTN in atrial arrhythmogenesis susceptibility. [score:1]
Modulation of miR-29 and miR-200 alters cardiac action potential determinants. [score:1]
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[+] score: 50
miR-29a, miR-144, miR-150, miR-192 and miR-320 showed an up-regulation from that of control samples whereas miR-30d, miR-146a and miR-182 showed down-regulation. [score:7]
miRNAs such as miR-144, miR-29a and miR-192 that were up-regulated in both IFG and T2D patients (Table S8) are predicted to target IRS1, AKT2 and INSR respectively. [score:6]
miR-29a and miR-320 that have been previously found to show altered expression in diabetic mo dels [34], [49], [50], also showed a significant up-regulation in the T2D samples in our study. [score:6]
Marginal expression levels were observed for miR-182 (−1.267±0.26) and miR-29a (1.351±0.23) which inversely correlated to their respective predicted mRNA targets FOXO1 and AKT2 respectively. [score:5]
Up-regulation of miR-29a/b observed in diabetic animal mo dels has also been shown to induce insulin resistance in cell culture [34]. [score:4]
In all five sources, miR-144, miR-150, miR-192, miR-29a and miR-320a were found to be highly up-regulated. [score:4]
The eight miRNAs (miR-144, miR-146a, miR-150, mR-182, miR-192, miR-29a, miR-30d and miR-320) which were previously identified in the rat study showed similar expression in the patients' blood miRNAs. [score:3]
Besides miR-192 [35] and miR-29a [34] which have previously been shown to be implicated in diabetes, we have also observed an approximately linear relationship between miR-144 expression and increasing glycaemic status (from IFG to T2D). [score:3]
miR-29a, miR-30d, miR-150 and miR-320 are all highly expressed in adipose, skeletal muscle and liver tissues with lower abundance in pancreas. [score:3]
The authors investigated the expression of seven diabetes-related miRNAs (miR-9, miR-29a, miR-30d, miR-34a, miR-124a, miR-146a and miR-375), four (miR-29a, miR-30d, miR-175 and miR-146a) of which were also found to be dysregulated in our study. [score:2]
We have also identified eight important miRNAs (miR-144, miR-146a, miR-150, miR-182, miR-192, mir-29a, miR-30d and miR-320) that could participate in the regulation of insulin signaling as well as useful in distinguishing different stages of diabetes progression. [score:2]
Employing miRNA microarray and stem-loop real-time RT-PCR, we identify four novel miRNAs, miR-144, miR-146a, miR-150 and miR-182 in addition to four previously reported diabetes-related miRNAs, miR-192, miR-29a, miR-30d and miR-320a, as potential signature miRNAs that distinguished IFG and T2D. [score:1]
Although our results were in conjunction with earlier studies which identified miR-192, miR-29a, miR-320 and miR-30d to be potential key players in the pathogenesis of T2D, we do observe differences in the recent study reported by Zampetaki et al [20]. [score:1]
Among these eight miRNAs, four of them namely miR-192 [35], miR-29a [34], miR-30d [49] and miR-320a [50], [51] had previously been reported in earlier studies and our results were consistent with them. [score:1]
Association of miR-192 [35], miR-29a [34] and miR-320 [50], [51] in T2D has been reported in previous studies and our study also shows similar results. [score:1]
Predictions: miR-144/ IRS1; miR-146a/ PTPN1; miR-150/ GLUT4 and CBL; miR-182/ FOXO1; miR-192/ INSR; miR-30d/ INS; miR-29a and miR-320/ AKT2. [score:1]
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17
[+] score: 47
KWV treatment reduced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), increased mRNA expression levels of the cyclin -dependent kinase inhibitor p21, reduced notch1 and hes1 transcription and up-regulated the miRNAs including miR-9, miR-29a and miR-181a. [score:9]
It is reported that reduced expression of miR-29a was found in patients and animal mo dels of neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease [71, 72]. [score:9]
Assessment of the miRNA expression levels in 2.5 μM of KWV -treated NSCs in the presence of mitogens using RT PCR showed that miR-9, miR-29a, and miR-181a expression were significantly up-regulated (1.44-, 1.51- and 1.34-fold, vs. [score:8]
Recently, it is reported that miR-29a knockin in mesenchymal stem cells (MSCs) significantly down-regulated the expression of REST and generated neurons from MSCs, suggesting that miR-29a is involved in neuronal differentiation [76]. [score:7]
Thus, up-regulation of miR-29a upon KWV treatment may also play critical roles in KWV -induced neurogenesis. [score:4]
The miScript PCR system (Qiagen) was used to analyze the expression of miRNAs, including rno-miR-9, rno-miR-29a, rno-miR-124 and rno-miR-181a, according to the manufacturer’s instructions. [score:3]
KWV treatment increased the expression of miR-29a, providing a possible mechanism of increased neuronal survival during NSC differentiation. [score:3]
A recent study reiterated the role of miR-29 in neuronal survival by knocking down miR-29 in the mouse brain [73]. [score:2]
miR-29 knockdown resulted in massive neuronal death in the hippocampus and cerebellum. [score:2]
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In addition, accumulating evidence suggests that miR-29 downregulation inhibits dilation of aneurysms and is helpful in an early fibrotic response at the aortic wall by increasing target gene expression in murine mo dels of experimental aneurysms and human aneurysm tissues [29]. [score:10]
In recent years, some studies have reported that miR-29 is a novel diagnostic biomarker and therapeutic target for cancer, because it plays an important role in angiogenesis, invasion, and metastasis of tumors by regulating MMP2 expression [30]. [score:6]
Moreover, in the chronic kidney disease mice, miR-29a/b was significantly suppressed in muscle [48]. [score:5]
Furthermore, all members of the miR-29 family were downregulated in myocardial tissue adjacent to the infarct and during cardiac fibrosis after acute myocardial infarction in mice and humans [28]. [score:4]
It has been reported that peripheral plasma levels of miR-29a in hypertrophic cardiomyopathy patients were significantly upregulated, when compared with a control group, and these levels correlated with both hypertrophy and fibrosis [27]. [score:3]
The miR-29 family (miR-29a, miR-29b-3p, and miR-29c) has been previously implicated in multiple pathological changes in cardiovascular diseases. [score:3]
Surprisingly, there was also a negative correlation between miR-29a and total MMP2 expression in human thoracic aortic aneurysm tissue [43]. [score:3]
), as shown in Figure 2. These data suggested that miR-29 may be involved in vascular calcification through mediation of MMP2 expression. [score:3]
To further characterize the mechanisms involving miR-29b-3p -mediated MMP2 expression, a luciferase assay was performed to determine whether miR-29 can directly target MMP2. [score:3]
The rat miR-29 family includes three members: miR-29a, miR-29b-3p, and miR-29c, whose dysregulation has been reported in many studies. [score:2]
In addition, the miR-29 family is involved in aneurysm development by mediating extracellular matrix protein synthesis, including Col1a1, Col3a1, Col5a1, and Eln. [score:2]
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[+] score: 40
The expression levels of miRNAs miR-107, miR-181c, miR-103, miR-101, miR-29a, miR-21 and miR-9 expression levels were down-regulated in the serum of diabetic rats and IOMe -injected rats (A). [score:8]
0172429.g005 Fig 5 The expression levels of miRNAs miR-107, miR-181c, miR-103, miR-101, miR-29a, miR-21 and miR-9 expression levels were down-regulated in the serum of diabetic rats and IOMe -injected rats (A). [score:8]
Our study demonstrated a significant down-regulation in miR-29a expression in brain and sera of induced rats with increased in BACE1 expression as well as Aβ levels in rat brains of T2DM. [score:8]
The expression levels of miR-107, miR-181c, miR-103, miR-101, miR-29a, miR-21 and miR-9 were significantly down regulated in the blood serum of diabetic and IOMe -injected rats (Fig 5A) whereas, the expression levels of these miRNAs are normally high. [score:6]
Moreover, miR-29 has target specific sites on BACE1 mRNA and its down-regulation increases AD progression [65]. [score:6]
Furthermore, miR-29a expression is inversely correlated with BACE1 and increased the amyloid in vitro production in neuronal cellular mo dels [64]. [score:3]
In contrast, NF-κB signaling transcriptionally repressed miR-29a/b [66]. [score:1]
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[+] score: 33
Based on the finding that the miR-29 family is expressed in the rat retina [14] and that one miRNA has several targets, we hypothesize that miR-29b could regulate the genes in the pro-apoptotic pathways that are involved in the apoptosis of the retinal neurons of STZ -induced diabetic rats. [score:6]
A: The firefly luciferase reporter construct (pISORAX plasmid) contains a partial-length 3′-UTR of RAX mRNA in the 5′ to 3′ orientation with respect to the firefly-luc open reading frame with the firefly luciferase start and stop codons and the potential miR-29 target site. [score:3]
The results of the computational analysis indicated that one of the miR-29 targets is RAX mRNA. [score:3]
The firefly luciferase start and stop codons and the potential miR-29 target site are also shown. [score:3]
The localization of the binding sites of these paralogs of miR-29 to on the RAX 3′-UTR overlap, and there is only a single target site on RAX for each miRNA studied. [score:3]
The computational prediction programs suggested that RAX is a target of the miR-29 family (miR-29a, miR-29b, and miR-29c), and miR-29b showed the highest score of prediction. [score:3]
We found that the three paralogs of miR-29 (miR-29a, miR-29b, and miR-29c) have a complementary sequence to the seed sequence on RAX with minor divergences (Figure 3B), suggesting that the three paralogs potentially target RAX mRNA. [score:3]
The retinas were dissected and used either for the analysis of RAX mRNA and miR-29 expression and protein analysis or processed for in situ hybridization and immunofluorescence. [score:3]
The expression profiles of miR-29a and miR-29c were similar to that found for miR-29b (data not shown). [score:3]
The bioinformatic algorithms TargetScan, miRanda, and FindTar were used to predict miR-29 binding sites in the 3′-UTR of RAX mRNA. [score:3]
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[+] score: 32
We observed that 1-day hypoxia down-regulated miR-29a expression, which is probably an adaptive compensation of the kidney for overcoming the hypoxic stress. [score:6]
Although UFP-512 treatment alone did not alter miR-29a levels, the addition of UFP-512 to the hypoxic kidney significantly downregulated the miR-29a expression to 40–60% of the control levels after both 1 and 5 days of hypoxia. [score:6]
The miR-29 family directly target at least 16 extracellular matrix genes and are relevant to renal and cardiovascular injury [29]– [31]. [score:4]
Following chronic exposure to hypoxia, miR-29a was upregulated by more than 100% as opposed to hypoxia alone. [score:4]
Relative miRNA expression levels of miR-351 and miR-29a in the kidney following either 1, 5, or 10 days of hypoxia as determined by quantitative RT-PCR. [score:3]
Recent research suggests that miR-29 inhibits cell proliferation and induces cell cycle arrest [32], modulates oxidative injury [33] and promote apoptosis through a mitochondrial pathway that involves Mcl-1 and Bcl-2 [28]. [score:3]
Several miRNAs (e. g., miR-29) that showed a dynamic change with hypoxic durations in this work regulate the process of oxidative stress and inflammation and are involved in regulation of apoptotic and survival signal pathways,. [score:3]
The addition of UFP-512 appeared to reduce the hypoxia-increased level of miR-29a (Figure 7). [score:1]
Furthermore, hypoxic exposure for an even longer duration, i. e., 10 days, significantly increased both miR-29a and miR-29b levels that can explain induction of renal injury under prolonged hypoxia. [score:1]
Interestingly, DOR activation decreases the level of miR-29a in all these scenarios, suggesting a potential for therapeutic utilization of DOR activation in hypoxic/ischemic renal injury. [score:1]
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In the present study, miR-29a and miR-34a were upregulated after IRI, and they were both downregulated by huMSC treatment. [score:7]
Senescence-related proteins (β-galactosidase, p21 [Waf1/Cip1], p16 [INK4a] and transforming growth factor beta 1) and microRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. [score:6]
Using qPCR, we found that the expression of some senescence-related miRs in kidney tissue (mainly miR-29a and miR-34a; Fig.   4e, f) on D2 was higher in IRI rats than in control rats (4.6 ± 1.1 vs 1.0 ± 0.3 and 8.7 ± 2.7 vs 1.0 ± 0.0, p = 0.05) although the expression of both was protected in IRI + huMSC rats (0.3 ± 0.2 and 0.7 ± 0.5, respectively, p < 0.05 and p = 0.05). [score:5]
Klotho deficiency and normal ageing may be associated with upregulation of miR-29a and miR-29b [34], and miR-29a is associated with inflammation as well [33]. [score:4]
e Bar graphs showing renal miR-29a expression. [score:3]
Members of the miR-29 family suppress the protein phosphatase PPM1D, increasing apoptosis [30], and may function as markers of senescence because they can reduce the levels of type IV collagen, potentially weakening the basal membrane in senescent tissues [28]. [score:3]
The miRs studied were miR-29a, miR-29b, miR-335 and miR-34a (Applied Biosystems; Thermo Fisher Scientific). [score:1]
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This study further showed that high glucose and insulin (which indicate insulin resistance) up-regulate the expression of miR-29a/b in adipocyte cell lines. [score:6]
They also suggest the over -expression of miR-29a/b inhibits insulin -induced glucose import in the same adipocyte cell lines. [score:5]
This is exactly comparable with the only previous study of miRNAs in T2D, which identified a 1.5 fold up-regulation of miR-29a, together with the paralogs 29b and 29c, in skeletal muscle from GK and Wistar rats (normoglycaemic controls)[19]. [score:4]
Among the other miRNAs showing robust differences between GK and BN rats was a 1.5 fold up-regulation of miR-29a in adipose tissue. [score:4]
Northern blot analysis confirmed the up-regulation of all three miR-29 paralogs in muscle, adipose tissue and liver. [score:4]
He et al. (2007) [19] profiled miRNA expression in skeletal muscle in the Goto-Kakizaki (GK) rat, a well-characterized mo del of T2D, and compared it to normal Wistar rats; miR-29 paralogs were found to be over-expressed in the GK rat. [score:2]
BN analysis within adipose tissue (FC = 1.97, P = 0.078, P [adjusted ]= 0.99), as did the previously reported miR-29a (FC = 1.51, P = 0.05, P [adjusted ]= 0.99). [score:1]
Taken together, these data support the involvement of miR-29a in insulin resistance and the insulin-signaling pathway. [score:1]
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24
[+] score: 25
The miR-29 family members are induced by estrogen and reduce fibrosis by inhibiting expression of collagens [43]. [score:5]
The role of the miR-29 family, including miR-29b, in fibrosis disease has been recently reviewed and additional targets appear to be collagens [59]. [score:5]
In addition, the miR-29 family members appear to play a significant role in the development of liver fibrosis, possibly through the regulation of collagen expression [59]. [score:5]
The expression of six (miR-29a, miR-29b, miR-29c, miR-34a, miR-375, and miR-466b-2*) was altered in both males and females (Table  1). [score:3]
As rats mature from adults to old-age, miRNAs involved in cell death, cell proliferation, and cell cycle (miR-29 family and miR-34a) were found to change expression. [score:3]
The miR-29 family and miR-34a, whose expression was altered in both older males and older females, are relatively well-studied miRNAs, and their roles in cell proliferation and apoptosis are established [75, 76]. [score:3]
In addition, miR-29 family members may be involved in susceptibility to fibrosis. [score:1]
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25
[+] score: 21
Our study also revealed a suppressed miR-29a level during disease progression of T2D in ZDF rats, but this was not significant and, therefore, not included in our candidate list. [score:5]
In diabetic nephropathy, the miRNA-29 family protects the kidney from fibrotic damage, and the DPP-4 inhibitor linagliptin has been shown to inhibit TGF-β -induced endothelial to mesenchymal transition (EndMT) by restoring the miRNA-29s’ levels [64]. [score:5]
However, for instance, miR-29a was found to be decreased during disease progression in our study, as expected, but did not reach the level of statistical significance. [score:3]
Bagge A. Clausen T. R. Larsen S. Ladefoged M. Rosenstierne M. W. Larsen L. Vang O. Nielsen J. H. Dalgaard L. T. MicroRNA-29a is up-regulated in β-cells by glucose and decreases glucose-stimulated insulin secretion Biochem. [score:3]
Therefore, both miR-29a and miR-375 could be assessed in future studies as potential translatable biomarkers. [score:3]
Nevertheless, the miR-29 family might serve as a candidate for monitoring of treatment effects. [score:1]
The eight circulating miRNAs, miR-29a, miR-34a, miR-375, miR-103, miR-107, miR-132, miR-142-3p and miR-144, and the two tissue-specific miRNAs, miR-199a-3p and miR-223, were identified to be significantly altered in T2D across a meta-analysis of controlled profiling studies [51]. [score:1]
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[+] score: 21
Remarkably, the main direction of changes of these genes (decrease in mRNA expression during maturation) is in agreement with the developmental increase of miR-29 expression under the assumption that miRNAs negatively regulate gene expression. [score:10]
The results of the qPCR experiments (Fig. 5) show a large increase of miR-29a, -29b, -29c, -1, -194, -195, -347 and a decrease of miR-134 expression during early postnatal development in muscular type vasculature corroborating the microarray data. [score:4]
Notably, previously published studies provide some information about possible interactions between developmentally regulated miRNAs and genes, for example, regarding the miR-29 family. [score:3]
One of the most strongly altered miRNA during postnatal development is the miRNA-29 family (miRNA-29a, -29b and -29c), that is associated with different signaling cascades. [score:2]
Therefore, the finding of an established interaction between miR-29 and structural genes reported in the previous literature and our observation of differently expressed miR-29 and mRNA for collagen and elastin strongly suggest a possible interaction between these miRNAs and the regulated structural genes in the vessel investigated in our study. [score:2]
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[+] score: 21
From P4 to P28, miRNAs displayed very similar expression between both progeny: 0–22 (<5%) miRNAs displayed differential expression and 0–7 of them (<2%) had expression differences higher than 3. Ratios of miR-7a-5p, miR-24-3p, miR-29-3p, miR-137-3p or miR-1843-5p expressions relatively to miR-124-3p expression calculated from RT-qPCR at P28 data matched those calculated from HTS data (Fig. 3B). [score:7]
Given the number of miRNAs and the limited quantity of material in individual ARC/MEs, we selected six miRNAs: miR-124a-3p which is wi dely expressed throughout brain 15, miR-29a/b-3p whose brain-specific knockdown results in neuronal cell death 16 17, miR-7a-5p and miR-137-3p which are expressed in hypothalamic nuclei including ARC 18, miR-24-3p and miR-1843-5p which are still poorly or not clearly documented. [score:6]
As the U6 snRNA was excluded from small RNA fractions and could not been used as an internal reference to quantify miRNA expressions, we quantified the expression of miR-7a-5p, miR-24-3p, miR-29-3p, miR-137-3p and miR-1843-5p relatively to that of miR-124-3p, at P4, P8, P14.4 and P21.4 relatively to P28, from RT-qPCR amplification or sequencing data (Fig. 3A). [score:5]
Expression of miR-7a-5p, miR-24-3p, miR-29-3p, miR-137-3p and miR-1843-5p were quantified relatively to those of miR-124-3p, and relatively to those of stage P28, by using the ΔΔCt method 25 and experimentally ascertained amplification efficiencies. [score:3]
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28
[+] score: 20
miR-29a/b also target several proteins involved in neurodegenerative diseases, including BACE1/β-secretase, of which elevated levels can lead to increased amyloid β-peptides in patients with sporadic Alzheimer’s disease (Hebert et al. 2008). [score:7]
One of the miRNAs displaying the greatest decrease in expression between ages, miR-298, also targets the BACE1 mRNA (Boissonneault et al. 2009), suggesting complementary roles between miR-298 and miR-29a/b in regulating this protein. [score:6]
MicroRNA miR-29b is known to increase during neuronal maturation and to inhibit apoptosis in neurons, and miR-29a/b both affect dendritic spine morphology (Kole et al. 2011; Lippi et al. 2011). [score:3]
The members of the miR-29 family showed the highest increase in expression level from younger to older animals (Fig.   1d; log fold-change (LFC) of up to 5.5 from P2/P9 to P23/P45). [score:3]
Three of the top five most significant miRNAs that increased from early to late age were members of the miR-29 family. [score:1]
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29
[+] score: 19
Our results demonstrated that GS-Rb1 suppressed the expression of mir-1 and mir-29a in the mo del group, which might be the microRNA targets of GS-Rb1 to protect cardiomyocytes from H/I injuries. [score:7]
Downregulation of mir-29 (mir-29a and mir-29c) by antisense inhibitor also protected H9c2 cardiomyocytes from simulated IR injury. [score:6]
The expression level of mir-1, mir-29a, and mir-208 was increased in the H/I group (5.9-, 3.4-, and 9.3-fold versus control, relatively), while that of mir-21 and mir-320 was significantly decreased (0.35- and 0.41-fold versus control, relatively). [score:3]
Compared with that of the control group, expressions of mir-1, mir-29a, and mir-208 obviously increased in the experimental mo del groups. [score:2]
Antagomirs against mir-29a or mir-29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to IR injury [28]. [score:1]
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30
[+] score: 19
MicroRNA-29 overexpression and knockdown studies in cardiac cells and other cell types have reported its inhibitory action on the TGF- β1 pathway (Cushing et al. 2011; Luna et al. 2011; Roderburg et al. 2011; Zhang et al. 2014). [score:5]
Angiotensin II also has been reported to regulate expression of microRNA-29 via Smads. [score:4]
In summary, as outlined in Fig. 10 our study provides evidence that elevated IS levels caused by renal damage secondary to MI has a direct effect of on the expression of and microRNA-29. [score:4]
MicroRNA-21 and microRNA-29 are among the most abundantly expressed microRNAs in heart and are known to regulate fibrosis by their action on mRNA of extracellular matrix proteins and TGF- β1 (van Rooij et al. 2008; Liang et al. 2012). [score:4]
Chronic angiotensin II infusion in wild-type mice resulted in significant reduction in microRNA-29 while in Smad3 knockout mice this reduction was prevented (Zhang et al. 2014). [score:2]
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[+] score: 17
Figure 5The effects of MIAT suppression on the expression of miR-29 and Sp1 in high glucose -induced rMC-1 cells(A) MIAT suppression significantly reversed the decreased expression of miR-29 induced by high glucose. [score:9]
The effects of MIAT suppression on the expression of miR-29 and Sp1 in high glucose -induced rMC-1 cells. [score:5]
miR-29b belongs to the miR-29 family, which acts as a tumour suppressor in many tumour researches. [score:3]
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[+] score: 17
Therefore, increased expression of miR-29 and miR-24 and reduced expression of miR-34, miR-130 and miR-378 may be responsible for the beneficial effects exerted by MSC-Exo. [score:5]
Previous studies have shown that enhanced expression of miR-29 prevented kidney fibrosis by reducing the expression of collagen [32]. [score:5]
The expression of miR-29 and miR-24, which positively regulate cardiac functions, was relatively high (Figure 3(a)). [score:4]
Our results showed high expression of miR-29 and miR-24 in both MSC-Exo and MSCs. [score:3]
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[+] score: 17
Park and colleagues [69] have shown that family members of miR-29 upregulate the expression of p53 through regulation of transcription of cdc42 and p85α in tumor cells and as such induce apoptosis. [score:7]
In addition miR-29a/b was shown to be involved in BACE-1 expression in patients with Alzheimer's disease [31]. [score:5]
Another recent study found that miR-29 family could regulate DNA methylation via DNA methyltransferase 3A and 3B transcriptional regulation [71]. [score:3]
Our findings that miR-29b is upregulated in astrocytes and neurons after ischemia in vitro opens the path for further investigations to the role of miR-29 in apoptosis in other forms of dementia that have been related to lacunar brain ischemia. [score:2]
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34
[+] score: 16
To replicate the findings obtained using TLDA array plate, we selected three miRNAs that were upregulated (mir-124, miR-218, miR-29a) and three, miRNAs that were downregulated (miR-146a, miR-200c, miR-155) based on their highest degree of significance by chronic CORT treatment and re-analyzed their expression individually by qPCR. [score:9]
As listed in Supplementary Table 6, these genes were predicted targets of miR-124, miR-101, miR-29a, miR-30e, miR-181c, miR-365 and miR-218. [score:3]
Several components of PI3 kinase signaling such as AKT3, PTEN, PIK3C2A and PIK3C2, which play critical roles in neurotrophin -mediated signaling and cell survival, [62] are targets of miR-29a, miR-101a, miR-124, miR-181c and miR-678. [score:3]
We confirmed this finding by analyzing the six most significant CORT -induced altered miRNAs (miR-218, miR-124, miR-29a, miR-146a, miR-200c, miR-155) by qPCR. [score:1]
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[+] score: 16
A simultaneous control experiment was carried out with the pri-mir-29a expression vector instead of the HongrES2 expression vector to determine the specificity of the IP experiments (Figure. [score:5]
Mir-29a was known to be endogenous in the PC1 cells and the Northern blot analysis showed that its expression was inhibited in both cells with siDCR RNAi as well, and its pre-miRNA forms were accumulated. [score:5]
Thus, a BlAST search was performed against the Sanger miRbase to determine identified miRNAs with sequence similar to that of mil-HongrES2; ron-mir-298 was the only one found to have about 50% homology with mil-HongrES2 in sequence and a very low expression ratio (about 10 [−4]) compared with the mir-29a signal in miRNA chips (data not shown) in rat epididymis (Figure 3D). [score:2]
Mir-29a expression was also detected as a control to show that the whole RNAi experiment was effective. [score:2]
The left panel shows a control experiment using a probe of a known mir-29a to demonstrate that the IP worked. [score:1]
To confirm that this phenomena was not due to the special cell line or the transfections operation, an unrelated microRNA, mir-29a, was tested as a control. [score:1]
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36
[+] score: 16
Upregulation or downregulation of miRNAs previously implicated in aGvHD pathogenesis such as the miR-17-92 cluster, miR-29a, miR-29b, miR-146a, or miR-155 did not reach significance in the NanoString analysis. [score:7]
Particular miRNAs associated with aGvHD include miRNAs that enhance T-cell activation, such as miR-155 (4, 10), miR-142 (11), miR-29a, miR-29b, and the miR-17-92 cluster (12), and miRNAs that repress T-cell activation, such as mir-146a (13), which is also upregulated in T regulatory cells (Tregs) (14). [score:5]
We found clear upregulation of miR-146a and miR-155, but not of miR-29a, miR-29b, miR-19b, or miR-20a in skin (Figure 4A and data not shown). [score:4]
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37
[+] score: 16
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-21, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-33a, hsa-mir-98, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-133a-1, mmu-mir-135a-1, mmu-mir-141, mmu-mir-194-1, mmu-mir-200b, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-203a, hsa-mir-211, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-200b, mmu-mir-300, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-141, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-21a, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-343, rno-mir-135b, mmu-mir-135b, hsa-mir-200c, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-33, mmu-mir-211, mmu-mir-29b-2, mmu-mir-135a-2, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-326, hsa-mir-135b, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-21, rno-mir-26b, rno-mir-27b, rno-mir-27a, rno-mir-29b-2, rno-mir-29b-1, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-33, rno-mir-98, rno-mir-126a, rno-mir-133a, rno-mir-135a, rno-mir-141, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-200b, rno-mir-203a, rno-mir-211, rno-mir-218a-2, rno-mir-218a-1, rno-mir-300, hsa-mir-429, mmu-mir-429, rno-mir-429, hsa-mir-485, hsa-mir-511, hsa-mir-532, mmu-mir-532, rno-mir-133b, mmu-mir-485, rno-mir-485, hsa-mir-33b, mmu-mir-702, mmu-mir-343, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, hsa-mir-300, mmu-mir-511, rno-mir-466b-1, rno-mir-466b-2, rno-mir-532, rno-mir-511, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466b-8, hsa-mir-3120, rno-mir-203b, rno-mir-3557, rno-mir-218b, rno-mir-3569, rno-mir-133c, rno-mir-702, rno-mir-3120, hsa-mir-203b, mmu-mir-344i, rno-mir-344i, rno-mir-6316, mmu-mir-133c, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-3569, rno-let-7g, rno-mir-29c-2, rno-mir-29b-3, rno-mir-466b-3, rno-mir-466b-4, mmu-mir-203b
Among their shared miRNAs, previous research showed that miR-29 is significantly down-regulated and expressed in mesenchymal cells in the lungs of bleomycin -treated mouse [43]. [score:6]
We used TargetScan and miRanda database queries to obtain miRNAs, which had higher targeting combined with N4bp2, namely, miR-200, miR-429, miR-29 and miR-30. [score:5]
Our qRT-PCR results show that the expression of miR-29 and MRAK088388 was highly correlated in lung tissue. [score:3]
Based on these results and preliminary analysis, MRAK088388 possibly regulated lung myofibroblast growth and subsequent collagen deposition by sponging miR-29, which could bind to N4bp2. [score:2]
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38
[+] score: 14
For example, rno-miR-1-3p, rno-let-7 family, rno-miR-29a-3p, rno-miR-133a-3p, rno-miR-499-5p and rno-miR-140-3p are most highly expressed in both HF and control group in our study, which was consistent with the previous studies that rno-miR-133, rno-miR-1 and rno-miR-499 are highly expressed in the heart[26], and miR-1, let-7 and miR-133 are highly expressed in the murine heart[27]. [score:7]
MicroRNA-29a suppresses cardiac fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway. [score:4]
The most highly expressed miRNAs were rno-miR-1-3p, rno-let-7 family, rno-miR-29a-3p, rno-miR-133a-3p, rno-miR-499-5p and rno-miR-140-3p in both HF and control group. [score:3]
[1 to 20 of 3 sentences]
39
[+] score: 14
MiRNAs exhibiting old-age expression included miR-21, miR-146a (Figure  6A,C), and members of the miR-29 family (miRa/b/c), which exhibit low expression at young age with increasing expression at older ages (78 and 104 weeks) (Figure  5J-L). [score:7]
The miRNAs showing the highest expression within this group were three members of the miR-29 family (miR-29b, miR-29a, and miR-29c). [score:3]
Furthermore, in diabetic conditions, expression levels of miR-195 and miR-29 have been shown to be elevated and reduced, respectively, in podocytes where they play a role in apoptosis and fibrosis [4]. [score:3]
MiR-29 family repression of DNA methylation activities in older animals would suggest multiple levels of epigenetic regulation. [score:1]
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40
[+] score: 14
Studies have shown that AET increases microRNA-29 expression in the heart and consequently decreases collagen expression and protein levels [24, 25]. [score:5]
To confirm the involvement of obesity-regulated microRNAs in pathological CH, we analyzed the cardiac microRNA-29 family (microRNA-29a, microRNA-29b and microRNA-29c), whose expression affects collagen content. [score:4]
The relative expression of COLIAI, COLIIIAI, ANF, α-MHC, α-actin skeletal, β-MHC, microRNA-1, microRNA-29a, microRNA-29b, and microRNA-29c was analyzed using real-time polymerase chain reactions (real-time PCR) as described previously [24]. [score:3]
The microRNA-29 family has been described to negatively regulate collagen content and to be highly responsive to AET [22, 24, 25]. [score:2]
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41
[+] score: 13
miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family and that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family. [score:7]
The expression levels of two miRNAs (rno-miR-29c and rno-miR-29a) were reduced in the mature rat cochleae. [score:3]
The inconsistency between Zhang’s report and our study suggested that miRNA patterns in the organ of Corti change with aging and that miRNAs such as miR-183 and miR29 play different roles in the development of organ of Corti in newborn, younger and older animals. [score:2]
miRNAs that increased mostly in the adult basilar membrane includes miR-296, mi-130b and miR-183 and that those that decreased mostly include miR-29c and miR-29a. [score:1]
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42
[+] score: 13
Inhibition of FGF signaling through SU5402 -treated primitive streak regions of chick embryos identified up-regulation of let-7b, miR-9, miR-19b, miR-107, miR-130b, miR-148a, miR-203, and miR-218 and down-regulation of miR-29a and miR-489 (Bobbs et al. 2012). [score:9]
In the lens system, miR-29a was up-regulated by FGF2. [score:4]
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43
[+] score: 12
It has been shown that miR-29, miR-15 and miR-107 are upregulated; while miR-124, miR-34 and miR-153 are downregulated in patients with AD (Delay et al., 2012; Lau et al., 2013). [score:7]
Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/β-secretase expression. [score:5]
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44
[+] score: 12
In the present study the mRNA microarray experiment showed that many of the targets of miR-29 were indeed significantly down-regulated, both in WKY and SHR. [score:6]
MiR-29 has previously been related to aging and dilation of the aorta, associated with down-regulation of extracellular matrix molecules [18]. [score:3]
Thus, maturation in both WKY and SHR vessels was associated with a prominent increase in expression of the miR-29 family. [score:3]
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45
[+] score: 12
More direct evidence comes from a study using a mouse mo del of peritoneal dialysis, in which microRNA-29 (miR-29) was identified to be an inhibitor of peritoneal fibrosis through suppression of TGF-β signaling pathway [29]. [score:6]
The role of miR-29 family members in various fibrotic diseases such as renal and liver fibrosis has been reported, and the results indicate that they function through modulation of collagen related gene expression and formation of extracellular matrix [51, 52]. [score:5]
miR-29b is a member of the miR-29 family which shares the same seed sequence. [score:1]
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46
[+] score: 11
In the mo del group, 17 miRNAs were downregulated, including miR-1, miR-133, miR-29, miR-126, miR-212, miR-499, miR-322, miR-378, and miR-30 family members, whereas the other 18 miRNAs were upregulated, including miR-21, miR-195, miR-155, miR-320, miR-125, miR-199, miR-214, miR-324, and miR-140 family members. [score:7]
Among these differentially expressed miRNAs, miR-1, miR-133, miR-29, miR-126, miR-499, miR-30, miR-21, miR-195, miR-155, miR-199, miR-214, and miR-140 have been reported to be related to MI [25– 36], while the other miRNAs have not been reported directly in MI. [score:4]
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47
[+] score: 11
We also identified differential expression of a number of miRNAs which target histone modification enzymes; miR-145 suppresses histone deacetylase 2 (HDAC2) [51], miR-129 is predicted to target HDAC2 mRNA and miR-29 targets HDAC4 mRNA [52]. [score:11]
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48
[+] score: 11
The analysis based on their fold changes showed a significant (P < 0.05) upregulation of miR-200c-3p (predicted to regulate IL-13 and VEGF-alpha), miR203a-3p (predicted to regulate IL-24 and PRKC α), miR29-3p (predicted to regulate TNFRS1A), and miR-21-5p (predicted to regulate NFk-B activity), in ocular tissues of LPS+RvD1 -treated rats compared to the vehicle+LPS group (Figure 4). [score:7]
Interestingly, upregulation of miR29-3p and miR-21-5p induced by RvD1, significant already at the lowest dose of 10 ng/kg, was concomitant with the decrease of TNF- α and NF- κB levels in the ocular tissue (Figures 5 and 6). [score:4]
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49
[+] score: 11
Moreover, the downregulation of miR-29, which is a modulator of ECM homeostasis [106], may induce the overexpression of key pro-regenerative matrix molecules, such as laminin, collagen, and fibronectin. [score:6]
In fact, according to previous studies [17], [18], [19], [21], [22], highly expressed microRNAs in the spinal cord or the CNS, such as miR-125b, miR-29a, miR-30b, and miR-9*, show sustained, high levels of expression before and after injury (see file S1), suggesting an overall preservation of the cell populations in the spinal cord. [score:5]
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50
[+] score: 11
S1 Fig The expression of MiR-29 was determined by qRT-PCR in the EDL muscle from 35 weeks old normal littermates (NL) and chronic kidney disease (CKD) rats. [score:4]
The expression of MiR-29 was determined by qRT-PCR in the EDL muscle from 35 weeks old normal littermates (NL) and chronic kidney disease (CKD) rats. [score:4]
We demonstrated in CKD skeletal muscle tissue there is higher stem cell activation (decreased Pax-7, increase MyoD) and differentiation (myogenin) with the lower expression of a pro-myogenic factor, miR-29. [score:3]
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51
[+] score: 10
Additionally, specific miRNAs such as miR-200a [26], miR-200c [27], miR-335 [28] and miR-29a [25] were identified to regulate epididymal development by targeting β-catenin, E-cadherin, Zeb1, Nasp and etc. [score:5]
Comparatively, the miR-29 family showed consistent regional expression [25] while the miR-200 family were differentially expressed. [score:5]
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52
[+] score: 10
Among myocardial infarction-regulated miRNA members, the miR-29 family (miR-29a, miR-29b copy 1 and copy 2, and miR-29c) is down-regulated in the peri-infarct region of the heart [8], which is associated with collagen production by fibroblasts, subsequent collagen deposition, and eventually leads to heart failure [11]. [score:5]
miR-29 overexpression in combination with the Tri-P may facilitate iPSC [NCX1+] migration and survival, as well as permit neovascularization of the infarct, leading to improvements in LV functional performance after the occurrence of ischemic heart disease. [score:5]
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53
[+] score: 10
Relative miRNA expression levels of miR-29a and miR-511 in the rat cortex following 1, 5 or 10 days of hypoxia with or without UFP-512 treatment. [score:3]
Note that miRNA expression levels of miR-29a and miR-511 were altered at discrete time points by hypoxia and/or UFP-512. [score:3]
The miR-29a expression was unaltered after 5 days (data not shown), but a significant 2-fold repression in response to hypoxia was detected after 10 days (Figure 5b). [score:3]
For example, UFP-512 reduced miR-29a levels by 50% in both normoxic and hypoxic backgrounds within the first 24 hours (Figure 5a). [score:1]
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54
[+] score: 7
The let-7d 27 and miR-29 28 down-regulation, and the miR-21 up-regulation 29 contribute to PF. [score:7]
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55
[+] score: 7
Pten is directly targeted by miR-486 [24], miR-29a [60], and miR-141 [61]. [score:4]
For example, it has been reported that miR-221 [15], miR-199a/b [16][17], miR-27b [18], miR-195 [11] and miR-34a/b/c [19] positively regulate cardiac hypertrophy, while miR-378 [9], miR-29 [20], miR-150 [11], miR-223 [21] and miR-1 [22] negatively regulate cardiac hypertrophy. [score:3]
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56
[+] score: 7
Importantly, the miR-29 family was exclusively downregulated in the frontal cortex, resulting in upregulation of methyltransferase DNMT3a [21, 23]. [score:7]
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57
[+] score: 7
In an elegant study, Van Rooij [14] showed that downregulation of miRNA-29 increased collagen expression and fibrosis in the heart after MI. [score:6]
Wang G, Kwan BC-H, Lai FM-M, Chow K-M, Li PK-T, Szeto C-C. Urinary miR-21, miR-29, and miR-93: novel biomarkers of fibrosis. [score:1]
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58
[+] score: 7
Since the expression of LOXL2 is also influenced by hypoxia,, and microRNAs (miR-26 and mIR-29), there are also other potential strategies for targeting LOXL2 expression or activity (Wong et al., 2014). [score:7]
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59
[+] score: 7
The extent of downregulation can be categorized into three groups: one retaining less than 5% of the basal miRNA level in naïve animal (miR-10a, -98); one maintaining 5~15% (miR-99, -124a, -183) and one showing more than 25% left (miR-29a, -134). [score:4]
This phenomenon was often seen during mRNA regulation [24] and the rebounded change will be brought back to the base level eventually, e. g. miR-29a and -134 in this study. [score:2]
We noticed that miR-29a, -99, -124a, and -134 in inflamed animals reached a much higher level than that in naïve animals. [score:1]
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60
[+] score: 6
Overexpression of miR-29a/b/c causes insulin resistance, similar to that of incubation with high glucose and insulin (23). [score:3]
He et al (23) reported an elevated expression of the miR-29 gene family in skeletal muscle, liver and adipose tissues of diabetic GK rats. [score:3]
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61
[+] score: 6
To validate microarray results, we further examined the expression of miRNAs using qRT-PCR in samples from Langendorff-perfused hearts undergoing the same protocol as in Fig.   1. We focused on 6 miRNAs, miR-30c-2, miR-29a-3p, miR-125a-3p, miR-139-3p, miR-320, and miR-324-3p, which role in cardioprotection is still unknown. [score:3]
Nevertheless, changes in the levels of miR-29a-3p, miR-30c-2, and miR-320 were not significantly affected by Ucn-1. To assess the endogenous expression of miR-125a-3p, miR-324-3p, and miR-139-3p, we treated isolated cardiac myocytes with different concentrations of Ucn-1 (2, 10 and 50 nM). [score:3]
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62
[+] score: 6
Comparing significantly deregulated miRNAs in the SL- and PH-group, we identified 10 miRNAs (rno-miR-100, rno-miR-105, rno-miR-1224, rno-miR-133a/b, rno-miR-383, rno-miR-466c, rno-miR-483, rno-miR-598-5p, and rno-miR-628) that showed similar expression changes in both groups at the same postoperative time point, while one miRNA (rno-miR-29a) was regulated in the opposite direction at the same time point. [score:6]
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63
[+] score: 6
miR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene. [score:6]
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64
[+] score: 6
For example, miR-29 expression is downregulated in human and murine liver fibrosis, which is mediated by TGF-β and other inflammatory signals [16]. [score:6]
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65
[+] score: 6
Overall, the expression patterns of miRNAs fell into four main categories: (1) Enriched in early embryonic stages, especially at E10 and E13 and decreased gradually during development (i. e. the rno-miR-181 family); (2) Enriched late postnatally, especially at P14 and P28, and tended to increase over time (i. e. rno-miR-29a and rno-miR-128); (3, 4) Peaked around neonatal stage (P0), either highest peak or lowest peak. [score:4]
The expression patterns of some miRNAs observed in our study are consistent with what were observed in previous studies by using the blot-array and Northern blot assays, i. e. miR-125b, miR-9, and miR-181a [6], as well as miR-29a, miR-138 and miR-92 [53]. [score:2]
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66
[+] score: 6
Another gene family that we evidenced prevalently expressed in the WBCs is mir-29 (mir-29a, mir-29b, mir-29c; p = 2.19 E-4). [score:3]
We found that miRNAs with higher expression in WBCs includes different miRNA families: mir-15, mir-17, mir-181, mir-23, mir-27 and mir-29 families. [score:3]
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67
[+] score: 6
et al. the miR2Epi pathway can be described as the regulatory process in which miR-29a regulates DNA methylation of FHIT and WWOX through directly targeting DNMT-3a and DNMT-3b (two important DNA methyltransferases). [score:6]
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68
[+] score: 5
Other miRNAs from this paper: rno-mir-29c-1, rno-mir-29c-2
In addition, microRNA-29a and -29c expression prevented collagen type I and III expression in the border and the remote regions of the myocardial infarction. [score:5]
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69
[+] score: 5
Similarly, miR-29a, miR-221 and miR-23b in this network seem to regulate the expression of Vimentin and SLUG indirectly through Caspase 7, AP-1 (activator protein 1) and PAK (p21 protein activated kinase 2). [score:5]
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70
[+] score: 5
Some of the deregulated miRNAs (miR-181, miR-26, miR-1, mir-29, miR-214, miR-126, and miR-499) are reported to be related to hypoxia, cell development, and cell growth [1, 5, 7, 25]. [score:3]
Recently, some miRNAs for example miR-21, miR-1, miR-216[10], and miR-29 family[11], were reported to be deregulated in myocardial infarction. [score:2]
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71
[+] score: 5
Validation of a selected few by qPCR identified 10 miRNAs - miR-133b-3p, miR-208b-3p, miR-21-5p, miR-125a-5p, miR-125b-5p, miR-126-3p, miR-210-3p, miR-29a-3p, miR-494-3p and miR-320a, that were significantly up-regulated in HF myocardium compared to normal controls. [score:3]
Similarly, MiR-29a is reported to be a key regulator of cardiac fibrosis and hypertrophy 38, 39, and miR-21 is enhanced in the fibroblasts of failing hearts [40]. [score:2]
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72
[+] score: 5
As shown in Figure  2, miRNAs known to be expressed at high level in beta-cells [26- 28], such as miR-7, miR-29a and miR-146a, were released in exosomes by MIN6B1 cells and human islets. [score:3]
The amount of miR-7, miR-29a and miR-146a recovered in exosomes was measured by qPCR and is expressed as percentage of the corresponding miRNA present inside MIN6B1 cells (A) or human islets (B). [score:1]
As expected, miR-7, miR-29a and miR-146a released by MIN6B1 cells were protected from confirming that they resided inside the exosomes (Figure  2C). [score:1]
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73
[+] score: 5
After normalizing the signal intensities for all miRNA expression levels, miR-124-3p, miR-9a-3p, miR-34a-5p, miR-9a-5p, miR-125b-5p, miR-let-7c-5p, miR-29a-3p, miR-23b-3p, miR-451-5p, and miR-30c-5p were the miRNAs expressed at the highest levels (Figure  1). [score:5]
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74
[+] score: 4
Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. [score:2]
Expression of MicroRNA-29 and collagen in cardiac muscle after swimming training in myocardial-infarcted rats. [score:2]
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75
[+] score: 4
miR-29a regulates vascular neointimal hyperplasia by targeting YY1. [score:4]
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76
[+] score: 4
Du Y Upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7 by miR-29 repression mediates vascular smooth muscle calcificationArterioscler. [score:4]
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77
[+] score: 4
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-137, mmu-mir-140, mmu-mir-150, mmu-mir-155, mmu-mir-24-1, mmu-mir-193a, mmu-mir-194-1, mmu-mir-204, mmu-mir-205, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-143, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-222, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-143, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-150, hsa-mir-193a, hsa-mir-194-1, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-34a, rno-mir-322-1, mmu-mir-322, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-140, rno-mir-350-1, mmu-mir-350, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-33, mmu-mir-222, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-375, mmu-mir-375, mmu-mir-133b, hsa-mir-133b, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-19b-1, rno-mir-19b-2, rno-mir-23a, rno-mir-24-1, rno-mir-24-2, rno-mir-25, rno-mir-27b, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-31a, rno-mir-32, rno-mir-33, rno-mir-34a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-106b, rno-mir-126a, rno-mir-135a, rno-mir-137, rno-mir-143, rno-mir-150, rno-mir-193a, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-204, rno-mir-205, rno-mir-222, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, mmu-mir-410, hsa-mir-329-1, hsa-mir-329-2, mmu-mir-470, hsa-mir-410, hsa-mir-486-1, hsa-mir-499a, rno-mir-133b, mmu-mir-486a, hsa-mir-33b, rno-mir-499, mmu-mir-499, mmu-mir-467d, hsa-mir-891a, hsa-mir-892a, hsa-mir-890, hsa-mir-891b, hsa-mir-888, hsa-mir-892b, rno-mir-17-2, rno-mir-375, rno-mir-410, mmu-mir-486b, rno-mir-31b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-499b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, hsa-mir-486-2, mmu-mir-126b, rno-mir-155, rno-let-7g, rno-mir-15a, rno-mir-196b-2, rno-mir-322-2, rno-mir-350-2, rno-mir-486, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
For instance, in the case of miR-29a, which has previously been implicated in androgen signaling within the mouse epididymis, the predominant product originated from the 3′ arm (miR-29a-3p) and was expressed at levels that were at least 30-fold higher than that of the alternative 5′ arm product (miR-29a-5p) (Fig 7A). [score:3]
These data accord with other tissues in which miR-29a-3p has also been shown to represent the predominant product generated from the mir-29a precursor (miRBASE). [score:1]
[1 to 20 of 2 sentences]
78
[+] score: 4
Dramatical down-regulation of miR-29 was observed in the region of the fibrotic scar after MI [31]. [score:4]
[1 to 20 of 1 sentences]
79
[+] score: 4
Recent studies have identified that many miRs [11], such as miR-1, miR-21, miR-29, miR-31, miR-143/145, and miR-221/222, play important roles in neointimal hyperplasia by regulating the functions of VSMCs. [score:2]
A number of miRs, such as, miR-1, miR-21, miR-29, miR-31, miR-143/145 and miR-221/222, were verified to be involved in neointimal hyperplasia by regulating the functions of VSMCs [11]. [score:2]
[1 to 20 of 2 sentences]
80
[+] score: 4
Gomes PR Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulationAm. [score:4]
[1 to 20 of 1 sentences]
81
[+] score: 4
We found common expression of 9 miRNAs (miR-132, miR-137, miR-139, miR-29a, miR-324, miR-352, miR-282, miR-146a, and miR-23a) when our data were compared to a data set describing miRNA expression 60 d after pilocarpine -induced status epilepticus [24]. [score:4]
[1 to 20 of 1 sentences]
82
[+] score: 4
For example, it has been proposed that a loss of specific miRNAs, such as the cluster miR-29a/b-1, can contribute to increased BACE1 and Aβ levels in sporadic Alzheimer’s disease [36]. [score:3]
If this is the case, then the increase in miR-29a expression seen in the BFMC-supplemented group could be advantageous against AD, nonetheless additional investigation is required. [score:1]
[1 to 20 of 2 sentences]
83
[+] score: 4
For instance, some miRNAs, such as miR-29, miR-21 and miR-221, has been reported to regulate tumor cell growth, apoptosis, migration and invasion by targeting proteins involved in those cellular pathways [7- 9]. [score:4]
[1 to 20 of 1 sentences]
84
[+] score: 3
We identified a group of mRNA and microRNA previously associated with amyloid-ß induced toxicity (e. g. Frp2 and Ppif), or implicated in Alzheimer’s disease processes, (miR-29 and miR-9) [35- 47], (Table  4). [score:3]
[1 to 20 of 1 sentences]
85
[+] score: 3
Melo S. T. F. Fernandes T. Baraúna V. G. Matos K. C. Santos A. A. Tucci P. J. F. Oliveira E. M. Expression of microRNA-29 and collagen in cardiac muscle after swimming training in myocardial-infarcted rats Cell. [score:3]
[1 to 20 of 1 sentences]
86
[+] score: 3
Other miRNAs from this paper: cel-let-7, cel-lin-4, hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-29a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-29b-1, mmu-mir-101a, mmu-mir-128-1, mmu-mir-9-2, mmu-mir-132, mmu-mir-138-2, mmu-mir-181a-2, mmu-mir-199a-1, hsa-mir-199a-1, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-128-1, hsa-mir-132, hsa-mir-138-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-138-1, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-29a, mmu-mir-29c, mmu-mir-92a-2, rno-let-7d, rno-mir-7a-1, rno-mir-101b, mmu-mir-101b, hsa-mir-181b-2, mmu-mir-17, mmu-mir-181a-1, mmu-mir-29b-2, mmu-mir-199a-2, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-128-2, hsa-mir-128-2, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-29c, hsa-mir-101-2, cel-lsy-6, mmu-mir-181b-2, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-7a-2, rno-mir-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-29b-2, rno-mir-29b-1, rno-mir-29c-1, rno-mir-92a-1, rno-mir-92a-2, rno-mir-101a, rno-mir-128-1, rno-mir-128-2, rno-mir-132, rno-mir-138-2, rno-mir-138-1, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-199a, rno-mir-181a-1, rno-mir-421, hsa-mir-181d, hsa-mir-92b, hsa-mir-421, mmu-mir-181d, mmu-mir-421, mmu-mir-92b, rno-mir-17-2, rno-mir-181d, rno-mir-92b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, mmu-mir-101c, mmu-let-7j, mmu-let-7k, rno-let-7g, rno-mir-29c-2, rno-mir-29b-3, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
Examination of the temporal clusters revealed that probes with similar sequences showed correlated expression, as exemplified by miR-181a, miR-181b, miR-181c, smallRNA-12 (Figure 4a) and miR-29a, miR-29b and miR-29c (Figure 4b), respectively. [score:3]
[1 to 20 of 1 sentences]
87
[+] score: 3
Overexpression of miR-34a, miR-146a, miR199a-5p or miR-29 in MIN6 cells negatively impacts on beta cell function [6]. [score:3]
[1 to 20 of 1 sentences]
88
[+] score: 3
A previous study suggested that miR-29 regulates liver fibrosis and together with TGF- β and nuclear factor- κB forms part of a signaling nexus in HSCs [40]. [score:2]
It has also been shown that hepatic levels of miR-29 are significantly increased in mice with CCl4 induced liver damage and also in the livers of patients with advanced fibrosis. [score:1]
[1 to 20 of 2 sentences]
89
[+] score: 3
Among these 21 differentially expressed miRNAs, 17 (miR-10b-5p, miR-223-3p, miR-208a-5p, miR-434-3p, miR-190a-5p, miR-30d-5p, miR-347, miR-493-5p, miR-29a-5p, miR-451-5p, miR-190b-5p, miR-466c-5p, miR-883-5p, miR-466b-1-3p, miR-21-3p, miR-3596c, miR3584-3p) were proven significant (P < 0.05) by qRT-PCR, one (miR-487b-3p) had a tendency to be significant (P = 0.06), and three (miR-138-2-3p, miR-1188-3p, miR-665) were not confirmed to be significant (Table  2). [score:3]
[1 to 20 of 1 sentences]
90
[+] score: 3
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-138-2, mmu-mir-181a-2, mmu-mir-182, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10a, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-181a-1, mmu-mir-297a-1, mmu-mir-297a-2, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-138-2, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-138-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, rno-mir-301a, rno-let-7d, rno-mir-344a-1, mmu-mir-344-1, rno-mir-346, mmu-mir-346, rno-mir-352, hsa-mir-181b-2, mmu-mir-10a, mmu-mir-181a-1, mmu-mir-29b-2, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-125b-1, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-30e, hsa-mir-362, mmu-mir-362, hsa-mir-369, hsa-mir-374a, mmu-mir-181b-2, hsa-mir-346, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-10a, rno-mir-15b, rno-mir-26b, rno-mir-29b-2, rno-mir-29b-1, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-34b, rno-mir-34c, rno-mir-34a, rno-mir-106b, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-138-2, rno-mir-138-1, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-181a-1, hsa-mir-449a, mmu-mir-449a, rno-mir-449a, mmu-mir-463, mmu-mir-466a, hsa-mir-483, hsa-mir-493, hsa-mir-181d, hsa-mir-499a, hsa-mir-504, mmu-mir-483, rno-mir-483, mmu-mir-369, rno-mir-493, rno-mir-369, rno-mir-374, hsa-mir-579, hsa-mir-582, hsa-mir-615, hsa-mir-652, hsa-mir-449b, rno-mir-499, hsa-mir-767, hsa-mir-449c, hsa-mir-762, mmu-mir-301b, mmu-mir-374b, mmu-mir-762, mmu-mir-344d-3, mmu-mir-344d-1, mmu-mir-673, mmu-mir-344d-2, mmu-mir-449c, mmu-mir-692-1, mmu-mir-692-2, mmu-mir-669b, mmu-mir-499, mmu-mir-652, mmu-mir-615, mmu-mir-804, mmu-mir-181d, mmu-mir-879, mmu-mir-297a-3, mmu-mir-297a-4, mmu-mir-344-2, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-493, mmu-mir-504, mmu-mir-466d, mmu-mir-449b, hsa-mir-374b, hsa-mir-301b, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-879, mmu-mir-582, rno-mir-181d, rno-mir-182, rno-mir-301b, rno-mir-463, rno-mir-673, rno-mir-652, mmu-mir-466l, mmu-mir-669k, mmu-mir-466i, mmu-mir-669i, mmu-mir-669h, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, mmu-mir-1193, mmu-mir-767, rno-mir-362, rno-mir-504, rno-mir-582, rno-mir-615, mmu-mir-3080, mmu-mir-466m, mmu-mir-466o, mmu-mir-466c-2, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466p, mmu-mir-466n, mmu-mir-344e, mmu-mir-344b, mmu-mir-344c, mmu-mir-344g, mmu-mir-344f, mmu-mir-374c, mmu-mir-466b-8, hsa-mir-466, hsa-mir-1193, rno-mir-449c, rno-mir-344b-2, rno-mir-466d, rno-mir-344a-2, rno-mir-1193, rno-mir-344b-1, hsa-mir-374c, hsa-mir-499b, mmu-mir-466q, mmu-mir-344h-1, mmu-mir-344h-2, mmu-mir-344i, rno-mir-344i, rno-mir-344g, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-692-3, rno-let-7g, rno-mir-15a, rno-mir-762, mmu-mir-466c-3, rno-mir-29c-2, rno-mir-29b-3, rno-mir-344b-3, rno-mir-466b-3, rno-mir-466b-4
As an example, this situation has been demonstrated for miR-29 released from cancer tissue and targeting skeletal muscle cells, which triggers cytopathic effect and cachexia [120]. [score:3]
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91
[+] score: 3
Hepatocyte growth factor (HGF) inhibits collagen I and IV synthesis in hepatic stellate cells by miRNA-29 induction. [score:3]
[1 to 20 of 1 sentences]
92
[+] score: 3
Combining in silico and in vivo studies, He et al identified a potential miR-29 target, insulin -induced gene 1 (INSIG1, or growth response protein CL-6) [17]. [score:3]
[1 to 20 of 1 sentences]
93
[+] score: 3
This result was consistent with previous reports that Smad3 signaling promotes renal fibrosis by inhibiting miR-29 [15, 38]. [score:3]
[1 to 20 of 1 sentences]
94
[+] score: 3
As shown in Table 2, we found increased expression of liver specific miRNAs in transdifferentiated hepatocytes, including miR-122a, miR-21, miR-22, miR-182, miR-29 and miR-30. [score:3]
[1 to 20 of 1 sentences]
95
[+] score: 3
MiR-29, miR-133 and miR-30c are the most strongly fibrosis -associated miRNAs targeting a number of extracellular-matrix-related mRNAs [31], [32]. [score:3]
[1 to 20 of 1 sentences]
96
[+] score: 3
Qi H Activation of AMPK attenuated cardiac fibrosis by inhibiting CDK2 via p21/p27 and miR-29 family pathways in ratsMol. [score:3]
[1 to 20 of 1 sentences]
97
[+] score: 3
In line with studies in mice and zebra fish, we found that especially miR-124a and miR-29a were highly abundant in all regions, whereas the expression levels for miR-9 were more moderate (data not shown) [7], [41]– [45]. [score:3]
[1 to 20 of 1 sentences]
98
[+] score: 3
Notably, it was the miR-29 isoform more expressed in this Ras -driven rat thyroid cell transformation system. [score:3]
[1 to 20 of 1 sentences]
99
[+] score: 3
miR-21, miR-155 and miR-221/222 have recently been shown to regulate AngII signaling in cardiac fibroblasts [14– 16] and in endothelial cells [17], while miR-29 regulates fibrotic pathways [18]. [score:3]
[1 to 20 of 1 sentences]
100
[+] score: 2
Several miRNAs including miR-140, miR-199a, mir-193 and mir-29a/29b control the anabolic and catabolic regulation in cartilage [42]. [score:2]
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