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

Marta Saura, Carlos Zaragoza, Wangsen Cao, Clare Bao, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Charles J. Lowenstein

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)806-813
Number of pages8
JournalCirculation Research
Volume91
Issue number9
DOIs
StatePublished - Nov 1 2002

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Nitric Oxide Synthase Type III
Transforming Growth Factors
Transcription Factors
Co-Repressor Proteins
Cytoplasm
Endothelial Cells

Keywords

  • Atherosclerosis
  • Endothelial cell
  • Hypoxia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Saura, M., Zaragoza, C., Cao, W., Bao, C., Rodríguez-Puyol, M., Rodríguez-Puyol, D., & Lowenstein, C. J. (2002). Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression. Circulation Research, 91(9), 806-813. https://doi.org/10.1161/01.RES.0000040397.23817.E5

Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression. / Saura, Marta; Zaragoza, Carlos; Cao, Wangsen; Bao, Clare; Rodríguez-Puyol, Manuel; Rodríguez-Puyol, Diego; Lowenstein, Charles J.

In: Circulation Research, Vol. 91, No. 9, 01.11.2002, p. 806-813.

Research output: Contribution to journalArticle

Saura, M, Zaragoza, C, Cao, W, Bao, C, Rodríguez-Puyol, M, Rodríguez-Puyol, D & Lowenstein, CJ 2002, 'Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression', Circulation Research, vol. 91, no. 9, pp. 806-813. https://doi.org/10.1161/01.RES.0000040397.23817.E5
Saura, Marta ; Zaragoza, Carlos ; Cao, Wangsen ; Bao, Clare ; Rodríguez-Puyol, Manuel ; Rodríguez-Puyol, Diego ; Lowenstein, Charles J. / Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression. In: Circulation Research. 2002 ; Vol. 91, No. 9. pp. 806-813.
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