Diverging targets mediate the pathological role of miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
Ni Zeng, Yuqing Huang, Yu-Min Yan, Zhi-Qin Hu, Zhuo Zhang, Jiaxin Feng, Ji-Shen Guo, Jie-Ning Zhu, Yong‐Heng Fu, Xipei Wang, Mengzhen Zhang, Jinzhu Duan, Xi‐Long Zheng, Jindong Xu, Zhi‐Xin Shan
Abstract
. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p.