MicroRNA?331 inhibits isoproterenol?induced expression of profibrotic genes in cardiac myofibroblasts via the TGF?/smad3 signaling pathway.

ABSTRACT: Cardiac fibrosis in the failing heart is modulated by activated myofibroblasts, and is a pathology marked by their deposition of extracellular matrix proteins. The TGF? signaling pathway is important in stimulating fibrosis and therefore seems an attractive new target for anti-fibrotic therapy. The relationship between ncRNAs and TGF? signaling pathway has been extensively studied. Here, we have provided several lines of evidence to prove that the fibrosis process could be regulated by miR-331 through targeting TGF? signaling. First, bioinformatics analysis and dual luciferase assay validated a direct interaction between the miR-331 and TGF?-R1 3'UTR sequence which results in the downregulation of TGF? signaling pathway. Second, miR-331 expression was inversely related to the expression of a number of genes which are involved in extracellular matrix (ECM) production and deposition processes, both in the in vivo and in vitro fibrosis models. Third, in cultured mouse and human cardiac myofibroblasts (CMyoFbs) under ISO treatment, overexpression of miR-331 decreased the expression level of fibrosis-related genes. Consistently, western blot analysis confirmed that miR-331 overexpression ended in both Smad3 and Col1A1 protein level reduction in mouse cardiac myofibroblasts. Finally, flow cytometry analysis, cyclin D1 and D2 gene expression analysis, and wound-healing assay confirmed the inhibitory effect of miR-331 against cell proliferation and migration in ISO-treated cardiac myofibroblasts. Taken together, accumulative results showed that miR-331 reduced the level of fibrosis-related proteins in cardiac myofibroblasts culture via regulating TGF? signaling pathway.

SUBMITTER: Yousefi F 

PROVIDER: S-EPMC7843612 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature