Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
J Cell Biochem. 2018 Sep;119(9):7235-7244. doi: 10.1002/jcb.26903. Epub 2018 May 15.
Cardiac remodeling is a common pathophysiological change associated with acute myocardial infarction (AMI). Recent evidence indicates that microRNAs are strong posttranscriptional regulators which play an important role in regulating the microenvironment of myocardial tissue after AMI. In this study, we sought to explore the potential role and underlying mechanism of miR-130 in AMI. H9c2 cells were cultured under hypoxic conditions to simulate myocardial infarction. The influence of aberrantly expressed miR-130 on H9c2 cells under hypoxia was also estimated with RT-PCR, western blot and enzyme-linked immunosorbent assay. Using bioinformatics methods, of miR-130 target genes were verified with luciferase reporter assay. Then, the effects of miR-130 on AMI were identified in an induced myocardial injury model in rats. The results show that miR-130 downregulation remarkably decreased hypoxia-induced inflammation and fibrosis related protein expression in H9c2 cells and reversed hypoxia-induced peroxisome proliferator-activated receptor γ (PPAR-γ) inhibition. A bifluorescein reporter assay further confirmed that PPAR-γ was a target gene of miR-130. This study verified that PPAR-γ has a cardioprotective effect by inhibiting NFκB-mediated inflammation and TGF-β1-mediated fibrosis. In vivo experiments confirmed that downregulation of miR-130 expression promotes PPAR-γ-mediated cardioprotective effects by suppressing inflammation and myocardial fibrosis. Taken together, these findings suggest that miR-130 knockdown alleviates infarction-induced myocardial injury by promoting PPAR-γ expression.
心脏重构是与急性心肌梗死（AMI）相关的一种常见的病理生理变化。最近的证据表明，miRNA 是强有力的转录后调控因子，在 AMI 后心肌组织的微环境调节中发挥重要作用。在本研究中，我们试图探讨 miR-130 在 AMI 中的潜在作用及其潜在机制。培养 H9c2 细胞在低氧条件下模拟心肌梗死。还通过 RT-PCR、western blot 和酶联免疫吸附试验评估了异常表达的 miR-130 对低氧下 H9c2 细胞的影响。利用生物信息学方法，通过荧光素酶报告基因实验验证了 miR-130 的靶基因。然后，在大鼠诱导性心肌损伤模型中确定了 miR-130 对 AMI 的影响。结果表明，miR-130 下调显著降低了 H9c2 细胞中低氧诱导的炎症和纤维化相关蛋白的表达，并逆转了低氧诱导的过氧化物酶体增殖物激活受体 γ（PPAR-γ）抑制。双荧光素酶报告基因检测进一步证实 PPAR-γ 是 miR-130 的靶基因。本研究通过抑制 NFκB 介导的炎症和 TGF-β1 介导的纤维化，验证了 PPAR-γ 通过抑制炎症和心肌纤维化发挥心脏保护作用。体内实验证实下调 miR-130 的表达通过抑制炎症和心肌纤维化促进 PPAR-γ 介导的心脏保护作用。综上所述，这些发现表明 miR-130 的下调通过促进 PPAR-γ 的表达来减轻梗死引起的心肌损伤。
