miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury.
miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury.
复制标题
miR-17-3p有助于运动诱导的心脏生长并预防心肌缺血再灌注损伤
作者：
Shi J;Bei Y;Kong X;Liu X;Lei Z;Xu T;Wang H;Xuan Q;Chen P;Xu J;Che L;Liu H;Zhong J;Sluijter JP;Li X;Rosenzweig A;Xiao J
据报道，有限的 microRNA（miRNA、miR）对于运动诱导的心脏生长是必需的，并且对于防止病理性心脏重塑至关重要。在这里，我们确定了 miR-17-92 簇的成员及其在两种不同的小鼠运动模型中的乘客 miRNA 表达，并发现 miR-17-3p 在这两种模型中均有所增加。 miR-17-3p 促进心肌细胞肥大、增殖和存活。 TIMP-3被确定为miR-17-3p的直接靶基因，而PTEN则被miR-17-3p间接抑制。体内抑制 miR-17-3p 可减弱运动诱导的心脏生长，包括心肌细胞肥大和心肌细胞增殖标志物的表达。重要的是，注射 miR-17-3p agomir 的小鼠在心脏缺血/再灌注损伤后免受不良重塑。总的来说，这些数据表明 miR-17-3p 有助于运动诱导的心脏生长并防止不良心室重塑。 miR-17-3p可能代表促进心脏缺血/再灌注后功能恢复的新治疗靶点。
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.