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微小 RNA-206 通过靶向 Gadd45β 保护大鼠心肌缺血再灌注损伤。

MicroRNA-206 Protects against Myocardial Ischaemia-Reperfusion Injury in Rats by Targeting Gadd45β.

机构信息

Department of Cardiovascular Diseases, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665# Kongjiang Road, Yangpu district, Shanghai 200092, P.R. China.

Department of Cardiovascular Diseases, The Frist Affiliated Hospital of Jiaxing University, Jiaxing 314000, P.R China.

出版信息

Mol Cells. 2017 Dec 31;40(12):916-924. doi: 10.14348/molcells.2017.0164. Epub 2017 Dec 14.

Abstract

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that Gadd45β (growth arrest DNA damage-inducible gene 45β) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of Gadd45β. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting Gadd45β.

摘要

微小 RNA 通过翻译抑制或降解其靶 mRNA 来广泛参与心血管疾病的发病机制。最近的研究表明,微小 RNA-206 在心肌缺血再灌注(I/R)损伤中起关键作用。然而,miR-206 在心肌 I/R 损伤中的作用尚不清楚。本研究旨在确定 miR-206 在心肌 I/R 损伤中的特定作用,并探讨其潜在的分子机制。我们的结果表明,与相应的对照组相比,大鼠 I/R 组和缺氧/复氧(H/R)处理的 H9c2 细胞中 miR-206 的表达水平显著降低。miR-206 的过表达可显著减小梗死面积并抑制 I/R 损伤诱导的心肌细胞凋亡。此外,生物信息学分析、荧光素酶活性和 Western blot 分析证实 Gadd45β(生长停滞 DNA 损伤诱导基因 45β)是 miR-206 的直接靶基因。此外,与 Gadd45β 下调相关,促凋亡相关基因如 p53、Bax 和 cleaved caspase3 的表达降低。总之,本研究表明,miR-206 通过靶向 Gadd45β 可保护心肌免受 I/R 损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4a4/5750710/b9c2aadbf529/molce-40-12-916f1.jpg

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