miR-130 aggravates acute myocardial infarction-induced myocardial injury by targeting PPAR-

被引：55

作者：

Chu, Xianglin ^{[1
]}

Wang, Yiqing ^{[1
]}

Pang, Liewen ^{[1
]}

Huang, Jiechun ^{[1
]}

Sun, Xiaotian ^{[1
]}

Chen, Xiaofeng ^{[1
]}

机构：

[1] Fudan Univ, Dept Cardiothorac Surg, Huashan Hosp, Urumqi Middle Rd, Shanghai 200040, Peoples R China

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 2018年 / 119卷 / 09期

基金：

中国国家自然科学基金;

关键词：

acute myocardial infarction; inflammation; miR-130; myocardial fibrosis; PPAR-; CARDIAC FIBROSIS; GAMMA; HYPOXIA; INFLAMMATION; ACTIVATION; PATHWAY; CANCER;

D O I：

10.1002/jcb.26903

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (PPAR-) inhibition. A bifluorescein reporter assay further confirmed that PPAR- was a target gene of miR-130. This study verified that PPAR- has a cardioprotective effect by inhibiting NFB-mediated inflammation and TGF-1-mediated fibrosis. In vivo experiments confirmed that downregulation of miR-130 expression promotes PPAR--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- expression.

引用

页码：7235 / 7244

页数：10

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