EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model

doi:10.1016/j.yjmcc.2015.02.029

科研成果详情

题名	EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model
作者	Liang, Dandan1; Zhong, Peng 1,2; Hu, Jie 1; Lin, Feng 3; Qian, Yuanyuan1; Xu, Zheng1; Wang, Jingying1; Zeng, Chunlai 2; Li, Xiaokun1; Liang, Guang1
发表日期	2015-05
发表期刊	JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Epidermal growth factor receptor Diabetic cardiomyopathy Oxidative stress ROS EGFR inhibitor
其他关键词	GROWTH-FACTOR RECEPTOR ; ENDOPLASMIC-RETICULUM STRESS ; DYSFUNCTION ; MECHANISMS ; GLUCOSE ; METALLOTHIONEIN ; PHOSPHORYLATION ; TRANSACTIVATION ; MITOCHONDRIA ; TYPE-1
摘要	Diabetes mellitus is strongly associated with cardiomyopathy. The underlying mechanisms for the development of diabetic cardiomyopathy are complex and not completely understood. Recent studies showed that epidermal growth factor receptors (EGFRs) are involved in diabetes-induced cardiac injury. However, the role of EGFR in the diabetic heart has yet to be confirmed. The aim of the present study is to further determine the role of EGRF in the pathogenesis of diabetic heart injury. The type 1 diabetic mice induced by streptozotocin were treated with EGFR inhibitors (AG1478 and 451) for 8 weeks, respectively. It was observed that diabetes induced phospohorylation of EGFR and AKT, increased cardiac ROS levels, and ultimately led to cardiac remodeling including cardiac hypertrophy, disorganization, apoptosis, and fibrosis, while all these molecular and pathological alterations were attenuated by the treatment with EGFR inhibitors. In vitro, either pharmacological inhibition of EGFR/AKT or sh-RNA silencing of EGFR significantly inhibited high concentration glucose (HG)-induced ROS generation and subsequently cell apoptosis in both cardiac H9C2 cells and primary rat cardiomyocytes, respectively. The ROS reduction by EGFR inhibitor was associated with the decreased NADPH oxidase activity and expression in H9c2 cells. HG-induced cardiomyocyte injuries were also reduced by NAC, an inhibitor of ROS. This study provides evidence that EGFR has a key role in the pathogenesis of STZ-induced diabetic cardiac damage and remodeling via ROS generation, and suggests that EGFR may be a potential target in treating diabetic cardiomyopathy. (C) 2015 Elsevier Ltd. All rights reserved.
资助项目	Natural Science Funding of China [21272179, 81200572]; High-level Innovative Talent Funding of Zhejiang Department of Health [2010-190-17, 2012-197-19]; Zhejiang Key Group in Scientific Innovation [2010R50042]
出版者	ELSEVIER SCI LTD
出版地	OXFORD
ISSN	0022-2828
EISSN	1095-8584
卷号	82 页码:63-74
DOI	10.1016/j.yjmcc.2015.02.029
页数	12
WOS类目	Cardiac & Cardiovascular Systems ; Cell Biology
WOS研究方向	Cardiovascular System & Cardiology ; Cell Biology
WOS记录号	WOS:000354145700009
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	25758431
SCOPUSEID	2-s2.0-84924759050
通讯作者地址	[Liang, Guang]Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Molecular Biology;Cardiology and Cardiovascular Medicine
引用统计	被引频次：47[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/12520
专题	药学院（分析测试中心）附属第一医院_妇科药学院（分析测试中心）_生物有机与药物化学研究中心其他_附属第五医院（丽水市中心医院）
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University,Lishui, Zhejiang,323000,China; 3.Department of Gynaecology, The 1st Affiliated Hospital of Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
第一作者单位	生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Liang, Dandan,Zhong, Peng,Hu, Jie,et al. EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2015,82:63-74.
APA	Liang, Dandan., Zhong, Peng., Hu, Jie., Lin, Feng., Qian, Yuanyuan., ... & Liang, Guang. (2015). EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 82, 63-74.
MLA	Liang, Dandan,et al."EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 82(2015):63-74.