Micro RNA ‐503 promotes angiotensin II‐induced cardiac fibrosis by targeting Apelin‐13

作者：Yuhong Zhou, Lin Deng, Dandan Zhao, Lanlan Chen, Zhen Yao, Xiaowei Guo, Xue Liu, Lifang Lv, Bing Leng, Wei Xu, Guo‐Fen Qiao, Hongli Shan · 发表于：Journal of Cellular and Molecular Medicine · 年份：2016 · DOI：10.1111/jcmm.12754 · 被引用次数：78 · 研究领域：Apelin-related biomedical research、Nuclear Receptors and Signaling、Cardiovascular, Neuropeptides, and Oxidative Stress Research

Cardiac fibrosis is a major cause of heart failure. MicroRNAs (miRs) are important epigenetic regulators of cardiac function and cardiovascular diseases, including cardiac fibrosis. This study aimed to explore the role of miR-503 and its mechanisms in regulating cardiac fibrosis. miR-503 was found up-regulated in the mouse LV tissues subjected to transverse aortic constriction (TAC) and in neonatal cardiac fibroblasts (CFs) cultured with Angiotension II. The role of miR-503 in regulating CF cell proliferation and/or collagen production in mice neonatal CFs were determined using an MTT assay and RT-PCR respectively. Forced expression of miR-503 increased the cellular proliferation and collagen production in mice neonatal CFs. The effects were abrogated by cotransfection with AMO-503 (a specific inhibitor of miR-503). Injection of antagomiR-503 elevated cardiac function and inhibited the expression of connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β in the TAC mice. Additional analysis revealed that Apelin-13 is a direct target of miR-503, as the overexpression of miR-503 decreased the protein and mRNA expression levels of Apelin-13. In the CFs with pre-treatment of AngII, we transfected AMO-503 into the cells treated with siRNA-APLN. siRNA-APLN abolished the effects of AMO-503 on the production of collagen I and III and the expression of TGF-β and CTGF. Furthermore, pre-treatment of CFs with Apelin-13 (1-100 nmol/l) inhibited angiotensin II-mediate...