Involvement of Alphavbeta5 Integrin in the Establishment of Autocrine Tgf-beta Signaling in Dermal Fibroblasts Derived from Localized Scleroderma.
From: Department of Dermatology, Faculty of Medicine, University of Tokyo, Kumamoto University, Kumamoto, Japan.
The Journal of investigative dermatology
- Publish Date: Aug 2006
- ISSN: 0022-202X
- Volume: 126
- Issue: 8
- Pages: 1761-9
- Medium: Print
- Language: English
- Citation (JAMA): Asano Yoshihide, Ihn Hironobu, Jinnin Masatoshi, et al. Involvement of Alphavbeta5 Integrin in the Establishment of Autocrine Tgf-beta Signaling in Dermal Fibroblasts Derived from Localized Scleroderma.. J. Invest. Dermatol. Aug 2006;126:1761-9
Abstract
Localized scleroderma (LSc) is a connective tissue disorder limited to skin and subcutaneous tissue, which may share pathogenic processes with systemic sclerosis (SSc). We previously demonstrated that upregulated expression of integrin alphavbeta5 might contribute to autocrine TGF-beta signaling in SSc fibroblasts. Based on these data, we presently focused on alphavbeta5 and assessed its involvement in pathogenesis of LSc. We initially demonstrated that LSc fibroblasts might be activated by the stimulation of autocrine TGF-beta. Consistent with SSc fibroblasts, expression levels of alphavbeta5 were elevated in LSc fibroblasts in vitro and in vivo. Anti-alphavbeta5 antibody partially reversed expression levels of type I procollagen and MMP-1 and constitutive DNA-Smad3 binding in LSc fibroblasts. In LSc fibroblasts pretreated with antisense TGF-beta1, exogenous latent TGF-beta1 stimulation increased expression of type I procollagen in an alphavbeta5-dependent manner. The luciferase activities of TMLC cells, Mv1Lu cells stably expressing a portion of the plasminogen activator inhibitor 1 promoter, co-cultured with LSc fibroblasts were significantly elevated compared with those co-cultured with normal fibroblasts and were significantly reduced in the presence of anti-alphavbeta5 antibody. Anti-alphavbeta5 antibody reversed the myofibroblastic features of LSc fibroblasts. These results indicate that upregulated expression of alphavbeta5 contributes to autocrine TGF-beta signaling in LSc fibroblasts.
Mesh Headings (Keywords): Antibodies, Autocrine Communication, Biopsy, Cells, Cultured, Collagen Type I, DNA-Binding Proteins, Dermis, Female, Fibroblasts, Fluorescent Antibody Technique, Humans, Integrins, Male, Matrix Metalloproteinase 1, Membrane Proteins, Receptors, Vitronectin, Scleroderma, Localized, Smad3 Protein, Transforming Growth Factor beta, Transforming Growth Factor beta1
Check for Full Text / PubMed Unique Identifier (PMID): 16675963
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.