Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression

被引：64

作者：

Saura, M

Zaragoza, C

Cao, WS

Bao, C

Rodríguez-Puyol, M

Rodríguez-Puyol, D

Lowenstein, CJ ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21205 USA

[2] Univ Alcala de Henares, Dept Physiol, Madrid, Spain

[3] Hosp Univ Principes de Asturias, Madrid, Spain

[4] Fdn Ctr Nacl Invest Cardiovasc, Madrid, Spain

[5] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21218 USA

来源：

CIRCULATION RESEARCH | 2002年 / 91卷 / 09期

关键词：

endothelial cell; hypoxia; atherosclerosis;

D O I：

10.1161/01.RES.0000040397.23817.E5

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Transforming growth factor-beta (TGF-beta) increases expression of endothelial nitric oxide synthase (eNOS), although the precise mechanism by which it does so is unclear. We report that Smad2, a transcription factor activated by TGF-beta, mediates TGF-beta induction of eNOS in endothelial cells. TGF-beta induces Smad2 translocation from cytoplasm to nucleus, where it directly interacts with a specific region of the eNOS promoter. Overexpression of Smad2 increases basal levels of eNOS, and further increases TGF-beta stimulation of eNOS expression. Ectopic expression of Smurf, an antagonizer of Smad2, decreases Smad2 expression and blocks TGF-beta induction of eNOS. Because Smad2 can interact with a variety of transcription factors, coactivators, and corepressors, Smad2 may thus act as an integrator of multiple signals in the regulation of eNOS expression.

引用

页码：806 / 813

页数：8

共 63 条

[1] Endothelial cytosolic proteins bind to the 3' untranslated region of endothelial nitric oxide synthase mRNA: Regulation by tumor necrosis factor alpha [J].