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 journalArticlepeer-review

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

Keywords

  • Atherosclerosis
  • Endothelial cell
  • Hypoxia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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