Molecular mechanism of fibronectin gene activation by cyclic stretch in vascular smooth muscle cells.

Published

Journal Article

Fibronectin plays an important role in vascular remodeling. A functional interaction between mechanical stimuli and locally produced vasoactive agents is suggested to be crucial for vascular remodeling. We examined the effect of mechanical stretch on fibronectin gene expression in vascular smooth muscle cells and the role of vascular angiotensin II in the regulation of the fibronectin gene in response to stretch. Cyclic stretch induced an increase in vascular fibronectin mRNA levels that was inhibited by actinomycin D and CV11974, an angiotensin II type 1 receptor antagonist; cycloheximide and PD123319, an angiotensin II type 2 receptor antagonist, did not affect the induction. In transfection experiments, fibronectin promoter activity was stimulated by stretch and inhibited by CV11974 but not by PD123319. DNA-protein binding experiments revealed that cyclic stretch enhanced nuclear binding to the AP-1 site, which was partially supershifted by antibody to c-Jun. Site-directed mutation of the AP-1 site significantly decreased the cyclic stretch-mediated activation of fibronectin promoter. Furthermore, antisense c-jun oligonucleotides decreased the stretch-induced stimulation of the fibronectin promoter activity and the mRNA expression. These results suggest that cyclic stretch stimulates vascular fibronectin gene expression mainly via the activation of AP-1 through the angiotensin II type 1 receptor.

Full Text

Duke Authors

Cited Authors

  • Tamura, K; Chen, YE; Lopez-Ilasaca, M; Daviet, L; Tamura, N; Ishigami, T; Akishita, M; Takasaki, I; Tokita, Y; Pratt, RE; Horiuchi, M; Dzau, VJ; Umemura, S

Published Date

  • November 2000

Published In

Volume / Issue

  • 275 / 44

Start / End Page

  • 34619 - 34627

PubMed ID

  • 10930408

Pubmed Central ID

  • 10930408

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.m004421200

Language

  • eng