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

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“…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%

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

Yuan

Chen

et al. 2017

Cell Physiol Biochem

191

140

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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.

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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

191

140

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“…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

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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.

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“…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

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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.

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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

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