Amphiregulin promotes cardiac fibrosis post myocardial infarction by inducing the endothelial-mesenchymal transition via the EGFR pathway in endothelial cells

被引：20

作者：

Liu, Liang ^{[1
]}

Song, Shuai ^{[3
]}

Zhang, Ya Ping ^{[1
]}

Wang, Di ^{[1
]}

Zhou, Zhong'e ^{[1
]}

Chen, Yu ^{[1
]}

Jin, Xian ^{[1
]}

Hu, Cui Fen ^{[2
]}

Shen, Cheng Xing ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Cardiol, 600 Yishan Rd, Shanghai 200233, Peoples R China

[2] Fudan Univ, Minhang Hosp, Dept Ultrasound Med, 170 Xin Song Rd, Shanghai 201199, Peoples R China

[3] Shanghai Jiao Tong Univ, Affiliated Xinhua Hosp, Dept Cardiol, Sch Med, Shanghai, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2020年 / 390卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Amphiregulin; EndMT; Myocardial infarction; Cardiac fibrosis; EGFR pathway; EPIDERMAL-GROWTH-FACTOR; PROLIFERATION; INVASIVENESS; CONTRIBUTES; DYSFUNCTION; FIBROBLASTS; EXPRESSION; DISEASE;

D O I：

10.1016/j.yexcr.2020.111950

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The endothelial-mesenchymal transition (EndMT) plays a key role in the development of cardiac fibrosis (CF) after acute myocardial infarction (AMI). The results of our previous study showed that amphiregulin (AR) expression was enhanced after MI. However, the role of AR on EndMT post MI remains unknown. This study aimed to elucidate the impact of AR on EndMT post MI and the associated molecular mechanisms. AR expression was markedly enhanced in infarct border area post MI, and endothelial cells were one of the primary cell sources of AR secretion. Stimulation with AR promoted endothelial cell proliferation, invasion, migration, collagen synthesis and EndMT. In addition, EGFR and downstream gene expression was significantly enhanced. In vivo, EndMT was significantly inhibited after lentivirus-AR-shRNA was delivered to the myocardium post MI. In addition, silencing AR ameliorated cardiac function by decreasing the extent of CF. Furthermore, the levels of EGFR pathway components in endothelial cells extracted from infarct border myocardium were all significantly decreased in lentivirus-AR-shRNA-treated MI mice. Our results demonstrate that AR induces CF post MI by enhancing EndMT in endothelial cells. Thus, targeting the regulation of AR may provide a potentially novel therapeutic option for CF after MI.

引用

页数：15

共 52 条

[1]

AKAGI M, 1995, CANCER, V75, P1460, DOI 10.1002/1097-0142(19950315)75:6+<1460::AID-CNCR2820751512>3.0.CO

[2]

2-O

[3] Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension [J].