MicroRNA-146a protects against myocardial ischaemia reperfusion injury by targeting Med1
MicroRNA-146a protects against myocardial ischaemia reperfusion injury by targeting Med1
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MicroRNA-146a 通过靶向 Med1 预防心肌缺血再灌注损伤
DOI：
10.1186/s11658-019-0186-5
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发表时间：
2019
影响因子：
8.3
通讯作者：
Changqian Wang
中科院分区：
文献类型：
--
作者：
Tiantian Zhang;Yiwen Ma;Lin Gao;Chengyu Mao;Huasu Zeng;Xiaofei Wang;Yapin Sun;Jianmin Gu;Yue Wang;Kan Chen;Zhihua Han;Yuqi Fan;Jun Gu;Junfeng Zhang;Changqian Wang
背景心肌缺血再灌注损伤（MIRI）是临床上的一个难题，它可能涉及多种microRNA。本研究旨在探讨内源性microRNA-146 a在心肌缺血再灌注中的作用及其可能的靶基因。在再灌注后的WT小鼠的心肌中评估MicroRNA-146 a表达。比较KO和WT小鼠的心功能、心肌梗死面积和原位细胞凋亡。采用基因芯片技术检测microRNA-146 a的靶基因，采用qRT-PCR和双荧光素酶报告基因检测技术进行验证。Western blotting检测目的基因及相关信号分子的表达水平。A rescue study was used for further testing.ResultsMicroRNA-146 a上调1小时后再灌注。microRNA-146 a缺乏会降低心脏功能，增加心肌梗死和细胞凋亡。基因芯片检测到19个凋亡基因在KO小鼠中表达上调。qRT-PCR和双荧光素酶检测证实Med 1是microRNA-146 a的靶基因之一。在KO小鼠中由Med 1编码的TRAP 220被上调，伴随着Bax/Bcl 2的放大比率和增加的裂解的caspase-3。结论microRNA-146 a对MIRI具有保护作用，其机制可能部分由靶基因Med 1介导，与凋亡信号通路有关。
BackgroundMyocardial ischaemia reperfusion injury (MIRI) is a difficult problem in clinical practice, and it may involve various microRNAs. This study investigated the role that endogenous microRNA-146a plays in myocardial ischaemia reperfusion and explored the possible target genes.MethodsMIRI models were established in microRNA-146a deficient (KO) and wild type (WT) mice. MicroRNA-146a expression was evaluated in the myocardium of WT mice after reperfusion. The heart function, area of myocardium infarction and in situ apoptosis were compared between the KO and WT mice. Microarray was used to explore possible target genes of microRNA-146a, while qRT-PCR and dual luciferase reporter assays were used for verification. Western blotting was performed to detect the expression levels of the target gene and related signalling molecules. A rescue study was used for further testing.ResultsMicroRNA-146a was upregulated 1 h after reperfusion. MicroRNA-146a deficiency decreased heart function and increased myocardial infarction and apoptosis. Microarray detected 19 apoptosis genes upregulated in the KO mice compared with the WT mice. qRT-PCR and dual luciferase verified that Med1 was one target gene of microRNA-146a. TRAP220, encoded by Med1 in the KO mice, was upregulated, accompanied by an amplified ratio of Bax/Bcl2 and increased cleaved caspase-3. Inhibition of microRNA-146a in H9C2 cells caused increased TRAP220 expression and more apoptosis under the stimulus of hypoxia and re-oxygenation, while knockdown of the increased TRAP220 expression led to decreased cell apoptosis.ConclusionsMicroRNA-146a exerts a protective effect against MIRI, which might be partially mediated by the target gene Med1 and related to the apoptosis signalling pathway.