Document Detail


Estrogen attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of osteopontin production in vascular smooth muscle cells.
MedLine Citation:
PMID:  10869268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Previous in vitro studies have suggested that estrogen attenuates the vascular injury response by modulating vascular smooth muscle cell (VSMC) expression of soluble factor(s) directing migration of adventitial fibroblasts. Previous in vivo studies have established a role for osteopontin (OPN) and its integrin receptors after vascular injury. In this study, we examined OPN expression in activated VSMCs, its modulation by estrogen, and its effects on adventitial fibroblast migration. In addition, the relative functional roles of beta(1)- and beta(3)-integrin-matrix interactions were examined. METHODS AND RESULTS: Primary cultures of VSMCs and adventitial fibroblasts were derived from female Sprague-Dawley rats. Serum-activated VSMCs expressed high levels of OPN mRNA and secreted protein that was effectively inhibited by estrogen treatment (10(-7) mol/L). Compared with VSMCs, fibroblasts expressed similar levels of integrins alphanu and beta(1) and higher levels of integrin-beta(3). Exogenous OPN (5.0 to 40 microg/mL) directed fibroblast migration in a dose-dependent fashion. Anti-beta(3)-integrin antibody (F11) pretreatment markedly inhibited adventitial fibroblast migration directed by exogenous OPN or VSMC-conditioned medium in a dose-dependent manner. In contrast, anti-beta(1)-integrin antibody (Ha2/5) did not affect fibroblast migration. Similarly, pretreatment with either linear or cyclic RGD peptides (10 to 1000 micromol/L) inhibited fibroblast migration directed by OPN or VSMC-conditioned medium in a dose-dependent manner. CONCLUSIONS: These observations suggest that estrogen indirectly attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of OPN expression in VSMCs.
Authors:
G Li; Y F Chen; S S Kelpke; S Oparil; J A Thompson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  101     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-07-19     Completed Date:  2000-07-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2949-55     Citation Subset:  AIM; IM    
Affiliation:
Departments of Medicine, Vascular Biology and Hypertension Program, and Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / pharmacology
Antigens, CD / immunology,  physiology*
Cell Movement / drug effects,  physiology
Cells, Cultured
Estradiol / pharmacology
Estrogens / physiology*
Female
Fibroblasts / drug effects,  physiology*
Integrin beta3
Muscle, Smooth, Vascular / cytology,  drug effects,  metabolism*,  physiology
Oligopeptides / pharmacology
Osteopontin
Platelet Membrane Glycoproteins / immunology,  physiology*
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Sialoglycoproteins / antagonists & inhibitors*,  genetics,  pharmacology
Grant Support
ID/Acronym/Agency:
HL07457/HL/NHLBI NIH HHS; HL45990/HL/NHLBI NIH HHS; HL57270/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD; 0/Estrogens; 0/Integrin beta3; 0/Oligopeptides; 0/Platelet Membrane Glycoproteins; 0/RNA, Messenger; 0/Sialoglycoproteins; 0/Spp1 protein, rat; 106441-73-0/Osteopontin; 50-28-2/Estradiol; 99896-85-2/arginyl-glycyl-aspartic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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