MicroRNA-146a protects against myocardial ischaemia reperfusion injury by targeting Med1

Springer Science and Business Media LLC - Tập 24 Số 1 - 2019
Tiantian Zhang1, Yinjiao Ma2, Lin Gao1, Chengyu Mao1, Huasu Zeng1, Xiaofei Wang1, Yapin Sun1, Jianmin Gu3, Yue Wang1, Kan Chen1, Zhihua Han1, Yuqi Fan1, Jun Gu1, Junfeng Zhang1, Changqian Wang1
1Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
2Department of Anaesthesiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
3Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

Tóm tắt

Abstract Background Myocardial 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. Methods MIRI 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. Results MicroRNA-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. Conclusions MicroRNA-146a exerts a protective effect against MIRI, which might be partially mediated by the target gene Med1 and related to the apoptosis signalling pathway.

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