Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-β1–Induced Smooth Muscle Gene Expression Through Extracellular Signal–Regulated Kinase 1/2 Signaling Pathway Activation

Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-β1–Induced... Vascular Biology Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-1–Induced Smooth Muscle Gene Expression Through Extracellular Signal–Regulated Kinase 1/2 Signaling Pathway Activation Keiko Kawai-Kowase, Hiroko Sato, Yuko Oyama, Hiroyoshi Kanai, Mahito Sato, Hiroshi Doi, Masahiko Kurabayashi Objective—Transforming growth factor-1 (TGF1) and fibroblast growth factor (FGF) families play a pivotal role during vascular development and in the pathogenesis of vascular disease. However, the interaction of intracellular signaling evoked by each of these growth factors is not well understood. The present study was undertaken to examine the molecular mechanisms that mediate the effects of TGF1 and basic FGF (bFGF) on smooth muscle cell (SMC) gene expression. Methods and Results—TGF1 induction of SMC gene expression, including smooth muscle protein 22- (SM22) and smooth muscle -actin, was examined in the pluripotent 10T1/2 cells. Marked increase in these mRNA levels by TGF1 was inhibited by c-Src-tyrosine kinase inhibitors and protein synthesis inhibitor cycloheximide. Functional studies with deletion and site-directed mutation analysis of the SM22 promoter demonstrated that TGF1 activated the SM22 promoter through a CC(A/T-rich) GG (CArG) box, which serves as a serum response factor (SRF)– binding site. TGF1 increased SRF expression through an increase in transcription of the SRF gene. In the presence http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-β1–Induced Smooth Muscle Gene Expression Through Extracellular Signal–Regulated Kinase 1/2 Signaling Pathway Activation

Download PDF
7 pages

Loading next page...
 
/lp/wolters-kluwer-health/basic-fibroblast-growth-factor-antagonizes-transforming-growth-factor-HIBniT3d0l

References (29)

ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/01.ATV.0000136548.17816.07
pmid
15217807
Publisher site
See Article on Publisher Site

Abstract

Vascular Biology Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-1–Induced Smooth Muscle Gene Expression Through Extracellular Signal–Regulated Kinase 1/2 Signaling Pathway Activation Keiko Kawai-Kowase, Hiroko Sato, Yuko Oyama, Hiroyoshi Kanai, Mahito Sato, Hiroshi Doi, Masahiko Kurabayashi Objective—Transforming growth factor-1 (TGF1) and fibroblast growth factor (FGF) families play a pivotal role during vascular development and in the pathogenesis of vascular disease. However, the interaction of intracellular signaling evoked by each of these growth factors is not well understood. The present study was undertaken to examine the molecular mechanisms that mediate the effects of TGF1 and basic FGF (bFGF) on smooth muscle cell (SMC) gene expression. Methods and Results—TGF1 induction of SMC gene expression, including smooth muscle protein 22- (SM22) and smooth muscle -actin, was examined in the pluripotent 10T1/2 cells. Marked increase in these mRNA levels by TGF1 was inhibited by c-Src-tyrosine kinase inhibitors and protein synthesis inhibitor cycloheximide. Functional studies with deletion and site-directed mutation analysis of the SM22 promoter demonstrated that TGF1 activated the SM22 promoter through a CC(A/T-rich) GG (CArG) box, which serves as a serum response factor (SRF)– binding site. TGF1 increased SRF expression through an increase in transcription of the SRF gene. In the presence

Journal

Arteriosclerosis, Thrombosis, and Vascular Biology – Wolters Kluwer Health

Published: Aug 1, 2004

There are no references for this article.