MicroRNA-146a attenuates isoproterenol-induced cardiac fibrosis by inhibiting FGF2.

Cardiac fibrosis is a key factor of heart failure. Increasing evidence suggests that microRNAs (miRNAs/miRs) serve vital roles in the pathogenesis of cardiac fibrosis. The present study aimed to investigate the role of miR-146a-5p in isoproterenol (ISO)-induced cardiac fibrosis. Reverse transcription-quantitative PCR analysis demonstrated that miR-146a-5p expression was downregulated in ISO-treated rat heart tissue and ISO-induced cardiac fibroblasts (CFs). Conversely, the expression levels of basic fibroblast growth factor 2 (FGF2), collagen I and smooth muscle α-actin (α-SMA) were upregulated in ISO-treated rat cardiac tissue and CFs. Furthermore, viability and differentiation were inhibited in ISO-induced CFs transfected with miR-146a-5p mimics. Dual-luciferase reporter assay confirmed that miR-146a-5p targeted FGF2. Notably, FGF2 expression was suppressed following overexpression of miR-146a-5p, while FGF2 expression increased following miR-146a-5p knockdown. In addition, FGF2 knockdown suppressed the expression levels of FGF2, collagen I and α-SMA levels in CFs. Taken together, the results of the present study suggested that the miR-146a-5p/FGF2 pathway may be a novel therapy for cardiac fibrosis.