Oncotarget

Research Papers:

MicroRNA-126a-5p enhances myocardial ischemia-reperfusion injury through suppressing Hspb8 expression

Bimei Jiang, Yanjuan Liu, Pengfei Liang, Yuanbin Li, Zhenguo Liu, Zhongyi Tong, Qinglan Lv, Meidong Liu and Xianzhong Xiao _

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Oncotarget. 2017; 8:94172-94187. https://doi.org/10.18632/oncotarget.21613

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Abstract

Bimei Jiang1, Yanjuan Liu1, Pengfei Liang2, Yuanbin Li1, Zhenguo Liu3, Zhongyi Tong1, Qinglan Lv1, Meidong Liu1 and Xianzhong Xiao1

1Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, P. R. China

2Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, P. R. China

3Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Correspondence to:

Xianzhong Xiao, email: xiaoxianzhong@csu.edu.cn

Keywords: microRNA-126a-5p; myocardium; ischemia-reperfusion injury; Hspb8; H9C2 cells

Received: April 19, 2017    Accepted: August 23, 2017    Published: October 07, 2017

ABSTRACT

Previously, we found several genes are involved in myocardial ischemia-reperfusion (M-I/R) injury. In this report, we first developed a mouse model of M-I/R injury and demonstrated microRNA-126a-5p was associated with the M-I/R injury by using high-throughput microRNA expression analysis. We further investigated the expression and function of microRNA-126a-5p during mouse M-I/R injury. We observed high expression of microRNA-126a-5p in the M-I/R mice and increased levels of LDH and CK-MB (damage markers) in the serum. H2O2 and hypoxia/reoxygenation (H/R) treatment significantly increased the expression of microRNA-126a-5p in H9C2 cells in concentration- and time-dependent manners. Moreover, microRNA-126a-5p overexpression in H9C2 cells inhibited cell viability but increased LDH release and caspase 3 activity. Cardiac function analysis based on the measurements of hemodynamic parameters showed that microRNA-126a-5p expression ablation in M-I/R injured mice led to the reversal of the symptoms caused by M-I/R injury. Transesophageal echocardiography also revealed that the values of LVIDd and LVIDs were decreased while the values of LVFS% and LVEF% were increased in M-I/R injured mice after treatment with microRNA-126a-5p inhibitor, compared with the M-I/R injured mice treated with the control. Bioinformatic analysis demonstrated that Hspb8, a protective protein in myocardium, was the target of microRNA-126a-5p. Thus, these findings indicated that microRNA-126a-5p was up-regulated in mouse M-I/R model and promoted M-I/R injury in vivo through suppressing the expression of Hspb8, which may shed light on the development of potential therapeutic target for M-I/R injury.


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