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| Research article summary (published 29 Apr 2005): |
Connective tissue growth factor causes persistent proalpha2(I) collagen gene expression induced by transforming growth factor-beta in a mouse fibrosis model.
Full Abstract
Skin fibrotic disorders such as systemic sclerosis (SSc) are characterized by an excessive production of extracellular matrix (ECM) and understood to develop under the influence of certain growth factors. Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that is implicated in various fibrotic disorders and induced in fibroblasts after activation with transforming growth factor-beta (TGF-beta). To better understand the mechanisms of persistent fibrosis seen in SSc, we previously established an animal model of skin fibrosis induced by exogenous application of growth factors. In this model, TGF-beta transiently induced subcutaneous fibrosis and serial injections of CTGF after TGF-beta caused persistent fibrosis. To further define the mechanisms of skin fibrosis induced by TGF-beta and CTGF in vivo, we investigated in this study, the effects of growth factors on the promoter activity of the proalpha2 (I) collagen (COL1A2) gene in skin fibrosis. For this purpose, we utilized transgenic reporter mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase gene or a bacterial beta-galactosidase gene. Serial injections of CTGF after TGF-beta resulted in a sustained elevation of COL1A2 mRNA expression and promoter activity compared with consecutive injection of TGF-beta alone on day 8. We also demonstrated that the number of fibroblasts with activated COL1A2 transcription was increased by serial injections of CTGF after TGF-beta in comparison with the injection of TGF-beta alone. Furthermore, the serial injections recruited mast cells and macrophages. The number of mast cells reached a maximum on day 4 and remained relatively high up to day 8. In contrast to the kinetics of mast cells, the number of macrophages was increased on day 4 and continued to rise during the subsequent consecutive CTGF injections until day 8. These results suggested that CTGF maintains TGF-beta-induced skin fibrosis by sustaining COL1A2 promoter activation and increasing the number of activated fibroblasts. The infiltrated mast cells and macrophages may also contribute to the maintenance of fibrosis. Copyright 2004 Wiley-Liss, Inc.
Author information
Author/s: Chujo, Sonoko (S); Shirasaki, Fumiaki (F); Kawara, Shigeru (S); Inagaki, Yutaka (Y); Kinbara, Takuro (T); Inaoki, Makoto (M); Takigawa, Masaharu (M); Takehara, Kazuhiko (K);
Affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8641, Japan.
Journal and publication information
Publication Type: Journal Article
Journal: Journal of cellular physiology (J Cell Physiol), published in United States. (Language: eng)
Reference: 2005-May; vol 203 (issue 2) : pp 447-56
Dates: Created 2005/03/02; Completed 2005/06/01; Revised 2008/11/21;
PMID: 15605379, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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