HMGB1 mediates hyperglycaemia‐induced cardiomyocyte apoptosis via ERK/Ets‐1 signalling pathway

Journal of Cellular and Molecular Medicine

Wen-Ke Wang¹  Qing-Hua Lu²  Jia-Ning Zhang³  Ben Wang⁴  Xiang-Juan Liu¹  Feng-Shuang An¹  Wei-Dong Qin¹  Xue-Ying Chen¹  Wen-Qian Dong¹  Cheng Zhang¹  Yun Zhang¹ 

[1] The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China;Department of Cardiology, The Second Hospital of Shandong University, Jinan, China;School of Foreign Languages and Literature, Shandong University, Jinan, Shandong, China;Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

关键词: high glucose;    cardiomyocyte;    apoptosis;    diabetes;    HMGB1;    Ets‐1;   

DOI  :  10.1111/jcmm.12399

来源: Wiley

【 摘 要 】

Abstract

Apoptosis is a key event involved in diabetic cardiomyopathy. The expression of high mobility group box 1 protein (HMGB1) is up-regulated in diabetic mice. However, the molecular mechanism of high glucose (HG)-induced cardiomyocyte apoptosis remains obscure. We aimed to determine the role of HMGB1 in HG-induced apoptosis of cardiomyocytes. Treating neonatal primary cardiomyocytes with HG increased cell apoptosis, which was accompanied by elevated levels of HMGB1. Inhibition of HMGB1 by short-hairpin RNA significantly decreased HG-induced cell apoptosis by reducing caspase-3 activation and ratio of Bcl2-associated X protein to B-cell lymphoma/leukemia-2 (bax/bcl-2). Furthermore, HG activated E26 transformation-specific sequence-1 (Ets-1), and HMGB1 inhibition attenuated HG-induced activation of Ets-1 via extracellular signal-regulated kinase 1/2 (ERK1/2) signalling. In addition, inhibition of Ets-1 significantly decreased HG-induced cardiomyocyte apoptosis. Similar results were observed in streptozotocin-treated diabetic mice. Inhibition of HMGB1 by short-hairpin RNA markedly decreased myocardial cell apoptosis and activation of ERK and Ets-1 in diabetic mice. In conclusion, inhibition of HMGB1 may protect against hyperglycaemia-induced cardiomyocyte apoptosis by down-regulating ERK-dependent activation of Ets-1.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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