miR-10a-5p inhibits cardiac fibrosis by targeting the MRTF-A/TGF-β2 feedback loop.

Cardiac fibrosis is a significant contributor to cardiac dysfunction and heart disease. The present study investigated the role of miR-10a-5p in mitigating cardiac fibrosis, potentially through its regulation of Myocardin-related transcription factor A (MRTF-A). RNA sequencing of heart samples obtained from patients with rheumatoid heart disease (RHD) revealed a marked reduction in miR-10a-5p expression in RHD patients exhibiting cardiac fibrosis, which was accompanied by an elevation in MRTF-A expression. In in vitro models of fibrosis, including primary myocardial fibroblasts and NIH3T3 cells treated with TGF-β, miR-10a-5p was shown to suppress cellular proliferation, migration, and the expression of fibrosis markers such as COL1A2, ACTA2, and SM-22α, through the targeted inhibition of MRTF-A. MRTF-A was identified as a pivotal regulator of fibrosis, and the use of siRNA targeting MRTF-A, as well as the ROCK inhibitor Y27632, both reduced MRTF-A expression and its nuclear localization. Furthermore, MRTF-A was found to positively regulate TGF-β2 expression. In vivo, administration of miR-10a-5p resulted in an improvement in cardiac function and a reduction in cardiac fibrosis in a mouse model. These findings suggest that miR-10a-5p may serve as a potential interventional target for cardiac fibrosis by inhibiting MRTF-A.