MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Deng, Peng; Chen, Ling; Liu, Zheng; Wang, Sihua; Wu, Jie; Yao, Yufeng; Sun, Yuan; Huang, Xintang; Ren, Linyun; Zhang, Anchen; Wang, Ke; Wu, Chuangyan; Zhang, Yue; Xu, Xuezeng; Chen, Manhua

doi:10.1159/000445568

Cited by 41 publications

(39 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the past decade, numerous evidence has demonstrated the role of microRNAs in various pathophysiological processes, including cardiac fibrosis [17-20]. Among these fibrosis-related microRNAs, miR-21 was previously reported to play an important role in regulation of fibrosis in multiple tissues, such as kidney, liver and lung etc [25-27].…”

Section: Discussionmentioning

confidence: 99%

“…They act as negative regulators of gene expression by inhibiting mRNA translation or promoting mRNA degradation [15, 16]. Recently, key roles of miRNAs in various pathophysiological processes, including cardiac fibrosis, were reported in a number of studies, indicating a new mode of regulation of cardiac diseases [17-20]. For instance, miR-21 was demonstrated to be an important regulator in fibroblasts proliferation and fibrosis [21], and miR-29, miR-30 and miR-133 have been found to inhibit collagen expression [22, 23].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Yuan

Chen

et al. 2017

Cell Physiol Biochem

194

140

View full text Add to dashboard Cite

Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. Methods: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice. First, we explored the expression of miR-21 in the infarcted zone in mice model of MI via RT-qPCR. Next, we examined the effects of TGF-β1 on miR-21 expression in cardiac fibroblasts (CFs). Then, CFs were infected with miR-21 mimics or miR-21 inhibitors to investigate the effects of miR-21 on the process of CFs activation in vitro. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-21. At last, in-vivo study was done to confirm MiR-21 regulated myocardial fibrosis after MI in mice. Results: MiR-21 was up-regulated in the infarcted zone after MI in vivo. TGF-β1 treatment increased miR-21 expression in CFs. Overexpression of miR-21 promoted the effects of TGF-β1-induced activation of CFs, evidenced by increased expression of Col-1, α-SMA and F-actin, whereas inhibition of miR-21 attenuated the process of fibrosis. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that Smad7 is a direct target of miR-21. In addition, in-vivo study revealed that MiR-21 regulated myocardial fibrosis after MI in mice. Conclusion: These findings suggested that miR-21 has a critical role in CF activation and cardiac fibrosis after MI through via TGF-β/Smad7 signaling pathway. Thus, miR-21 promises to be a potential therapy in treatment of cardiac fibrosis after MI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Yuan

Chen

et al. 2017

Cell Physiol Biochem

194

140

View full text Add to dashboard Cite

show abstract

“…CFs are not only involved in extracellular matrix protein production, tissue repair, scar formation, inflammatory response, vasculogenesis, and tumorigenesis, but also have a role in myocardial remodeling, hypertensive heart disease, and heart failure [3,4]. CFs actively participate in the regulation of cardiac physiological and pathological processes and thus represent pertinent targets for pharmacological approaches for cardiac diseases, which may point to novel therapeutic strategies [5].…”

Section: Introductionmentioning

confidence: 99%

Effects of the Calcium-Activated Chloride Channel Inhibitors T16Ainh-A01 and CaCCinh-A01 on Cardiac Fibroblast Function

Tian

Wang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Calcium-activated chloride channels (CaCCs) regulate numerous physiological processes including cell proliferation, migration, and extracellular matrix secretion. T16Ainh-A01 and CaCCinh-A01 are selective inhibitors of CaCCs. But it is unknown whether these two compounds have functional effects on cardiac fibroblasts (CFs). Methods: Primary CFs were obtained by enzymatic dissociation of cardiomyocytes from neonatal rat hearts. Intracellular Ca²⁺ ([Ca²⁺]_i) and Cl^- ([Cl^-]_i) were measured using the fluorescent calcium indicators (Fluo-4 AM) and N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide respectively. The expression of anoctamin-1 (ANO1) and α-smooth muscle actin (α-SMA) was detected by quantitative RT-PCR, immunofluorescence, and western blotting. A hydroxyproline assay was used to examine collagen secretion. Cell proliferation, cell cycle distribution, and cell migration were assessed by Cell Counting Kit-8, flow cytometry, and Transwell assays, respectively. Results: ANO1 was preferentially expressed on the nuclear membrane and partially within intracellular compartments around the nucleus. T16Ainh-A01 and CaCCinh-A01 displayed different inhibitory effects on [Cl^-]_i in CFs. T16Ainh-A01 considerably decreased [Cl^-]_i in the nucleus, whereas CaCCinh-A01 reduced [Cl^-]_i in intracellular compartments around the nucleus, and both inhibitors exhibited a minimal effect on [Ca²⁺]_i in CFs. ANO1 and α-SMA expression levels were significantly repressed by CaCCinh-A01. T16Ainh-A01 showed a marked inhibitory effect on the mRNA levels of ANO1 and α-SMA, but had a negligible effect on ANO1 at the protein level. T16Ainh-A01 and CaCCinh-A01 led to the significant repression of cell proliferation, cell migration, and collagen secretion in CFs. Conclusion: Our findings indicate that T16Ainh-A01 and CaCCinh-A01 have the potential to inhibit the proliferation and collagen secretion of CFs and may serve as novel anti-fibrotic therapeutic drugs in the future.

show abstract

“…MicroRNAs (miRNAs), which are about 22–25 nucleotides in length, are a kind of non-coding single-stranded RNA molecule encoded by endogenous genes. They participate in gene regulation at the transcriptional level [13]. Each miRNA can regulate multiple target genes, while different miRNAs can also regulate the same target gene [14].…”

Section: Introductionmentioning

confidence: 99%

Regulation of MiR-146a and TRAF6 in the Diagnose of Lupus Nephritis

Zhu

Xue

2017

Med Sci Monit

View full text Add to dashboard Cite

BackgroundLupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). This study tested miR-146a and its target gene TRAF6 expression in LN patients and discussed their relationship with LN.Material/MethodsOne hundred twenty-eight LN patients and 30 healthy controls were enrolled in this study. MiR-146a and TRAF6 expression in peripheral blood mononuclear cells (PBMCs) were detected. Serum cytokines content was determined by ELISA. The diagnostic role of miR-146a and TRAF6 in LN activity was evaluated by ROC curve. The impact of miR-146a and TRAF6 on end-stage renal disease (ESRD) was compared by survival curve. The effect of miR-146a and TRAF6 on LN recurrence was analyzed.ResultsCompared with healthy controls, miR-146a expression was significantly reduced and TRAF6 was upregulated in LN patients. The expression was related to LN activity. MiR-146a expression was negatively correlated, whereas TRAF6 was positively correlated with serum IL-1β, IL-6, IL-8, and TNF-α activity. The area under the ROC curve (AUC) of miR-146a and TRAF6 on the diagnosis of LN was 0.821 and 0.897, respectively. The AUC of miR-146a and TRAF6 on LN activity differentiation was 0.921 and 0.872, respectively. Downregulation of miR-146a and upregulation of TRAF6 increased the incidence of ESRD progression. Downregulation of miR-146a and upregulation of TRAF6 elevated the possibility of recurrence within one year.ConclusionsMiR-146a declined, while TRAF6 increased in LN patients compared with healthy controls. Their expression can be used to effectively differentiate LN and evaluate activity. MiR-146a reduction and TRAF6 upregulation increased the possibility of ESRD progress and recurrence within one year.

show abstract

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Cited by 41 publications

References 56 publications

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Effects of the Calcium-Activated Chloride Channel Inhibitors T16Ainh-A01 and CaCCinh-A01 on Cardiac Fibroblast Function

Regulation of MiR-146a and TRAF6 in the Diagnose of Lupus Nephritis

Contact Info

Product

Resources

About