微小RNA-31的下调通过直接靶向蛋白激酶Cε（PKCε）来预防心脏缺血/再灌注损伤。
MiR-31 Downregulation Protects Against Cardiac Ischemia/Reperfusion Injury by Targeting Protein Kinase C Epsilon (PKCε) Directly.
作者信息
Wang Yongyi, Men Min, Yang Wengang, Zheng Hui, Xue Song
机构信息
Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Cell Physiol Biochem. 2015;36(1):179-90. doi: 10.1159/000374062. Epub 2015 Apr 30.
BACKGROUND
Various miRNAs have been shown to participate in cardiac ischemia/reperfusion injury (I/R). miR-31 was identified as the most strikingly upregulated miRNA after acute myocardial infarction; therefore, the underlying role and mechanism of miR-31 in cardiac I/R was investigated.
METHODS
miR-31 expression was detected after cardiac I/R in mice. The cardioprotective effect of miR-31 downregulation was assessed in vitro and in vivo. The functional target gene and its downstream molecule were determined.
RESULTS
miR-31 expression increased after I/R. miR-31 downregulation increased cell viability and SOD activity and decreased LDH activity and MDA content in vitro. Additionally, miR-31 downregulation alleviated myocardial infarct size in vivo. PKCε was identified as the functional target gene of miR-31, and NFκB was identified as its downstream molecule that was involved in the miR-31-mediated cardioprotective effect.
CONCLUSION
miR-31 expression increased throughout the cardiac I/R process, and miR-31 downregulation induced a cardioprotective effect via a miR-31/PKCε/NFκB-dependent pathway.
背景
多种微小RNA（miRNA）已被证明参与心脏缺血/再灌注损伤（I/R）。miR-31被确定为急性心肌梗死后上调最为显著的miRNA；因此，对miR-31在心脏I/R中的潜在作用及机制进行了研究。
方法
检测小鼠心脏I/R后miR-31的表达。在体外和体内评估下调miR-31的心脏保护作用。确定功能性靶基因及其下游分子。
结果
I/R后miR-31表达增加。下调miR-31可增加体外细胞活力和超氧化物歧化酶（SOD）活性，降低乳酸脱氢酶（LDH）活性和丙二醛（MDA）含量。此外，下调miR-31可减轻体内心肌梗死面积。蛋白激酶Cε（PKCε）被确定为miR-31的功能性靶基因，核因子κB（NFκB）被确定为参与miR-31介导的心脏保护作用的下游分子。
结论
在整个心脏I/R过程中miR-31表达增加，下调miR-31通过miR-31/PKCε/NFκB依赖性途径诱导心脏保护作用。
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