TY - JOUR
T1 - Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression
AU - Saura, Marta
AU - Zaragoza, Carlos
AU - Cao, Wangsen
AU - Bao, Clare
AU - Rodríguez-Puyol, Manuel
AU - Rodríguez-Puyol, Diego
AU - Lowenstein, Charles J.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Transforming growth factor-β (TGF-β) 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-β, mediates TGF-β induction of eNOS in endothelial cells. TGF-β 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-β stimulation of eNOS expression. Ectopic expression of Smurf, an antagonizer of Smad2, decreases Smad2 expression and blocks TGF-β 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.
AB - Transforming growth factor-β (TGF-β) 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-β, mediates TGF-β induction of eNOS in endothelial cells. TGF-β 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-β stimulation of eNOS expression. Ectopic expression of Smurf, an antagonizer of Smad2, decreases Smad2 expression and blocks TGF-β 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.
KW - Atherosclerosis
KW - Endothelial cell
KW - Hypoxia
UR - http://www.scopus.com/inward/record.url?scp=0036842491&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036842491&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000040397.23817.E5
DO - 10.1161/01.RES.0000040397.23817.E5
M3 - Article
C2 - 12411395
AN - SCOPUS:0036842491
SN - 0009-7330
VL - 91
SP - 806
EP - 813
JO - Circulation research
JF - Circulation research
IS - 9
ER -