Downregulation of miR-96 suppresses the profibrogenic functions of cardiac fibroblasts induced by angiotensin II and attenuates atrial fibrosis by upregulating KLF13.

Abstract

Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). MicroRNA-96 (miR-96) has been reported to be associated with pulmonary fibrosis and hepatic fibrosis. Nevertheless, the role of miR-96 in atrial fibrosis is still unclear. In our study, we showed that miR-96 is upregulated in human atrial tissues from AF patients and positively correlates with collagen I and collagen III levels. Knockdown of miR-96 reduced angiotensin II (Ang-II)-induced cardiac-fibroblast proliferation, migration, and collagen production, whereas ectopic expression of miR-96 yielded opposite results. Furthermore, we demonstrated that miR-96 represses KLF13 expression, subsequently promoting Ang-II-induced proliferation, migration, and collagen production in murine cardiac fibroblasts. Moreover, we observed that the knockdown of miR-96 attenuated the Ang-II-induced atrial fibrosis in a mouse model of AF. All the findings point to a potential target for the prevention or treatment of atrial fibrosis.