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

Journal of Molecular and Cellular Cardiology
Dandan LiangGuang Liang

Abstract

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...Continue Reading

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Citations

Apr 14, 2015·Journal of Molecular and Cellular Cardiology·Zheng Xu, Lu Cai
Mar 26, 2016·Molecular and Cellular Endocrinology·Shahzad KhanChanghua Wang
Jul 23, 2016·Journal of Cellular and Molecular Medicine·Yaqin ZhangXiao Han
Sep 8, 2016·Proteomics. Clinical Applications·Donatus O OnwuliPedro Beltran-Alvarez
Jan 4, 2017·The International Journal of Biochemistry & Cell Biology·Melissa E ReicheltJohn P Headrick
Sep 18, 2018·Clinical and Experimental Pharmacology & Physiology·Xin JuYi Wang
Apr 30, 2020·American Journal of Physiology. Cell Physiology·Jake S RussellJohn P Headrick
Dec 31, 2017·Pflügers Archiv : European journal of physiology·Vishal MaliSouad Belmadani
May 22, 2020·Circulation Research·Rebecca H Ritchie, E Dale Abel
Jul 18, 2018·Frontiers in Cellular Neuroscience·Hyun Woo LimArwa Kurabi
Nov 30, 2018·Molecular Medicine Reports·Qian WangYan Meng
Jan 7, 2016·American Journal of Physiology. Endocrinology and Metabolism·Tao BaiLu Cai
Dec 22, 2020·Journal of Cellular Physiology·Liang LiXi-Long Zheng
Jul 8, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fangfang LiQing Li

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