However, the precise molecular mechanism of FRA2 involved into myocardial I/R injury remains not well explored. Owing to these well-known transcriptional targets of FRA2 are proved to be up-regulated in the tissue fibrosis, FRA2 might function as a crucial driver of myocardial fibrosis. In addition, the level of FRA2 is up-regulation in the infarcted myocardial tissue and implicates in accelerating TGF-β transcription. Previous study indicates that FRA-2 mediates oxygen-sensitive induction of transforming growth factor-β (TGF-β) in cardiac fibroblasts. Consistent with FRA1, the FRA2 lacks C-terminal trans-activating domain. The phosphorylation of FRA2 increases itself DNA binding activity. Once formed, these complexes bind to activator protein 1 (AP-1) sites. FRA2 forms stabilized heterodimer complexes with Jun family members, including c-Jun, Jun-B and Jun-D. However, the roles miR-155 in H/R-induced cardiomyocytes apoptosis and the cardiac fibrosis have not been entirely evaluated.įos-related antigen 2 (FRA2) is a member of Fos family, which contains various immediate-early serum-inducible genes. Altogether, these results imply that therapeutic targeting miR-155 may benefit myocarditis patients. Pharmacological inhibition of miR-155-5p by anti-miRs (antisense oligonucleotides) successfully inhibits cardiac infiltration by monocyte/macrophages, improves cardiac function and attenuates myocardial damage during viral myocarditis (VM). In addition, miR-155 regulates cardiac fibrosis through TGF-β1-Smad2 signaling pathway, which suggests miR-155 may be a potential therapeutic target for preventing cardiac fibrosis. Overexpression of miR-155 in endothelial cell inhibits cells proliferation and re-endothelialization and thus increases the permeability of vascular endothelial. Previously research has suggested miR-155 to be closely associated with cardiovascular heart diseases. Substantial studies have demonstrated that miRNAs play core roles in the regulation of a variety of cellular processes, including cells growth, cellular apoptosis and fibrosis. MicroRNAs is a class of non-coding RNAs, which directly bind to the 3′-UTR region of target genes and induce the degradation of target genes or inhibit the translation of target protein. Thus, reveal the basic molecular mechanisms are urgent for the development effective strategies of myocardial ischemia/reperfusion injury. Suppression of myocardial cell apoptosis and myocardial fibrosis could effectively reduce the degree of myocardial injury caused by I/R as well as improve the survival in patients with heart failure. Ischemia/reperfusion (I/R) injury is one of the mainly causes in cardiomyocyte apoptosis and cardiac fibrosis. Altogether, our results demonstrated that miR-155-5p restrain H/R-induced both cellular apoptosis and fibrosis of cardiomyocytes, partly via directly inhibit FRA2. Moreover, knocked-down of FRA2 accelerated cell growth whereas suppressed the apoptosis and fibrosis in M6200 cells induced by H/R. Both the bioinformatics analysis and luciferase reporter assay demonstrated fos-related antigen 2 (FRA2) is one of the direct targets of miR-155-5p, and miR-155-5p negatively regulated the expression of FRA2 in M6200 cells. Over-expression of miR-155-5p inhibited H/R-induced apoptosis and the fibrosis of cardiomyocyte M6200 cells. Our results implied that H/R induced M6200 cells apoptosis and increased the expression of fibrosis-associated proteins, including collagen I, collagen II, collagen III and fibronectin, as well as decreased the level of miR-155-5p. In this study, cardiomyocyte (M6200 cells) were exposed to hypoxia/reoxygenation (H/R). ![]() Nevertheless, the behind mechanisms remain not well investigation. Substantive researches have demonstrated that microRNAs are involved in myocardial I/R injury. Myocardial ischemia/reperfusion (I/R) injury results in cardiomyocytes apoptosis and cardiac fibrosis, which accompanied with fibroblasts trans-differentiate to myofibroblasts and the deposition of collagen. Received: SeptemAccepted: NovemPublished: January 30, 2018 Keywords: hypoxia/reoxygenation cardiomyocyte apoptosis microRNA-155-5p FRA2 Ge Jin 1, Xue Qiang Guan 1, Jia Li 1 and Jun Ma 1ġThe Department of Cardiology, 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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