MiR-103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts.

Cardiac hypertrophy is a common pathological change frequently accompanied by chronic hypertension and myocardial infarction. Nevertheless, the pathophysiological mechanisms of cardiac hypertrophy have never been elucidated. Recent studies indicated that miR-103 expression was significantly decreased in heart failure patients. However, less is known about the role of miR-103 in cardiac hypertrophy. The present study was designed to investigate the relationship between miR-103 and the mechanism of pressure overload-induced cardiac hypertrophy. TRPV3 protein, cardiac hypertrophy marker proteins (BNP and β-MHC) and autophagy associated proteins (Beclin-1 and LC3-II) were up-regulated, as well as, miR-103 expression and autophagy associated proteins (p62) were down-regulated in cardiac hypertrophy models in vivo and in vitro respectively. Further results indicated that silencing TRPV3 or forcing overexpression of miR-103 could dramatically inhibit cell surface area, relative fluorescence intensity of Ca2+ signal and the expressions of BNP, β-MHC, Beclin-1 and LC3-II, but promote p62 expression. Moreover, TRPV3 protein was decreased in neonatal rat ventricular myocyte transfected with miR-103, but increased by AMO-103. Co-transfection of the miR-103 with the luciferase reporter vector into HEK293 cells caused a sharp decrease in luciferase activity compared with transfection of the luciferase vector alone. The miR-103-induced depression of luciferase activity was rescued by an AMO-103. These findings suggested that TRPV3 was a direct target of miR-103. In conclusion, miR-103 could attenuate cardiomyocyte hypertrophy partly by reducing cardiac autophagy activity through the targeted inhibition of TRPV3 signalling in the pressure-overloaded rat hearts.