Department of Pharmacology, Harbin Medical University-Daqing, Daqing, China.
J Cell Mol Med. 2019 Mar;23(3):1926-1939. doi: 10.1111/jcmm.14095. Epub 2019 Jan 3.
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 Ca 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.
心肌肥厚是一种常见的病理变化，常伴有慢性高血压和心肌梗死。然而，心肌肥厚的病理生理机制尚未阐明。最近的研究表明，miR-103 在心力衰竭患者中的表达显著降低。然而，miR-103 在心肌肥厚中的作用知之甚少。本研究旨在探讨 miR-103 与压力超负荷诱导的心肌肥厚机制之间的关系。TRPV3 蛋白、心肌肥厚标志物蛋白（BNP 和 β-MHC）和自噬相关蛋白（Beclin-1 和 LC3-II）在体内和体外的心肌肥厚模型中均上调，而 miR-103 表达和自噬相关蛋白（p62）下调。进一步的结果表明，沉默 TRPV3 或强制过表达 miR-103 可显著抑制细胞表面积、钙信号相对荧光强度以及 BNP、β-MHC、Beclin-1 和 LC3-II 的表达，但促进 p62 的表达。此外，miR-103 转染的乳鼠心室肌细胞中 TRPV3 蛋白减少，但 AMO-103 增加。将 miR-103 与荧光素酶报告载体共转染 HEK293 细胞，与单独转染荧光素酶载体相比，荧光素酶活性明显下降。miR-103 诱导的荧光素酶活性下降可被 AMO-103 挽救。这些发现表明 TRPV3 是 miR-103 的直接靶标。总之，miR-103 可通过靶向抑制压力超负荷大鼠心脏中的 TRPV3 信号，部分减轻心肌肥厚，减少心脏自噬活性。
