Department of Adult Cardiac Surgery, The People's Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital, Heart Center of Henan Provincial People's Hospital, Zhengzhou, China.
Department of Hepatobiliary, The People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
J Cell Biochem. 2019 Jun;120(6):10421-10433. doi: 10.1002/jcb.28327. Epub 2019 Jan 15.
microRNAs are an emerging class of molecules that regulate pathogenesis of cardiovascular diseases. Here we aim to elucidate the effects and mechanism of miR-135a, a previously reported regulator of ischemia-reperfusion (I/R) injury, in myocardial I/R injury. Quantitative real-time polymerase chain reaction analysis revealed that the expression level of miR-135a was significantly decreased both in the rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation. Overexpression of miR-135a in vivo markedly decreased the infarct size and inhibited the I/R-induced cardiomyocyte apoptosis. Overexpression of miR-135a in H9c2 also exerted antiapoptosis effects. Furthermore, bioinformatics analysis, luciferase activity, and the Western blot assay indicated that protein tyrosine phosphatase 1B (PTP1B) is a direct target of miR-135a. In addition, the expression of proapoptotic-related genes, such as p53, Bax, and cleaved caspase3, were decreased in association with the downregulation of PTP1B. In summary, this study demonstrates that miR-135a exerts protective effects against myocardial I/R injury by targeting PTP1B.
microRNAs 是一类新兴的分子，可调节心血管疾病的发病机制。在这里，我们旨在阐明 miR-135a 的作用及其机制，miR-135a 是先前报道的缺血再灌注 (I/R) 损伤的调节剂，在心肌 I/R 损伤中。定量实时聚合酶链反应分析显示，miR-135a 的表达水平在大鼠 I/R 组和缺氧/复氧的 H9c2 细胞中均显著降低。体内过表达 miR-135a 可显著减少梗死面积并抑制 I/R 诱导的心肌细胞凋亡。在 H9c2 中过表达 miR-135a 也具有抗凋亡作用。此外，生物信息学分析、荧光素酶活性和 Western blot 分析表明，蛋白酪氨酸磷酸酶 1B (PTP1B) 是 miR-135a 的直接靶标。此外，与 PTP1B 的下调相关，促凋亡相关基因如 p53、Bax 和 cleaved caspase3 的表达减少。总之，本研究表明，miR-135a 通过靶向 PTP1B 发挥对心肌 I/R 损伤的保护作用。
