miR-17-3p contributes to exercise-induced cardiac growth and protects against myocardial ischemia-reperfusion injury
Shi, Jing, Bei, Yihua, Kong, Xiangqing, Liu, Xiaojun, Lei, Zhiyong, Xu, Tianzhao, Wang, Hui, Xuan, Qinkao, Chen, Ping, Xu, Jiahong, Che, Lin, Liu, Hui, Zhong, Jiuchang, Sluijter, Joost P.G., Li, Xinli, Rosenzweig, Anthony, Xiao, Junjie
DOI: https://doi.org/10.7150/thno.15162
Theranostics 7 (3), p. 664-676
Abstract
Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling. Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both. miR-17-3p promoted cardiomyocyte hypertrophy, proliferation, and survival. TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p. Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation. Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury. Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling. miR-17-3p may represent a novel therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.