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Article
Blockade of endogenous transforming growth factor β signaling prevents up-regulated collagen synthesis in scleroderma fibroblasts: Association with increased expression of transforming growth factor β receptors
Article first published online: 28 FEB 2001
DOI: 10.1002/1529-0131(200102)44:2<474::AID-ANR67>3.0.CO;2-#
Copyright © 2001 by the American College of Rheumatology
1529-0131/asset/cover.gif?v=1&s=104d5c2bb8ef72deba26790b855af7ab80697a0e "Arthritis & Rheumatism")
Additional Information
How to Cite
Ihn, H., Yamane, K., Kubo, M. and Tamaki, K. (2001), Blockade of endogenous transforming growth factor β signaling prevents up-regulated collagen synthesis in scleroderma fibroblasts: Association with increased expression of transforming growth factor β receptors. Arthritis & Rheumatism, 44: 474–480. doi: 10.1002/1529-0131(200102)44:2<474::AID-ANR67>3.0.CO;2-#
Publication History
- Issue published online: 28 FEB 2001
- Article first published online: 28 FEB 2001
- Manuscript Accepted: 13 OCT 2000
- Manuscript Received: 19 JUL 2000
Funded by
- Ministry of Education, Japan. Grant Number: 10770391
- Research for Progressive Systemic Sclerosis project of the Ministry of Health and Welfare
- Shiseido Co., Ltd, Japan
- Lydia O'Learly Memorial Foundation, Japan
- Abstract
- Article
- References
- Cited By
Abstract
Objective
To elucidate the role of transforming growth factor β (TGFβ) in the increased expression of the collagen gene in scleroderma fibroblasts.
Methods
Dermal fibroblasts from 10 patients with diffuse systemic sclerosis (SSc) of recent onset and from 10 healthy individuals were studied. The production of active and total (active + latent) TGFβ1 levels from cultured dermal fibroblasts was measured using a TGFβ1 enzyme-linked immunosorbent assay system. Expression of the TGFβ type I and type II receptor proteins in dermal fibroblasts was determined by immunoblotting, and the level of expression of human α2(I) collagen messenger RNA (mRNA) was evaluated by Northern blot analysis. The transcriptional activity of the human α2(I) collagen gene was examined with chloramphenicol acetyltransferase (CAT) assays using the −772 COL1A2/CAT construct.
Results
SSc fibroblasts expressed increased levels of TGFβ type I and type II receptors but secreted amounts of TGFβ similar to those secreted by normal fibroblasts. The blockade of TGFβ signaling with anti-TGFβ antibodies or a TGFβ1 antisense oligonucleotide abolished the increased mRNA expression, as well as the up-regulated transcriptional activity of the human α2(I) collagen gene in SSc fibroblasts.
Conclusion
These results suggest that TGFβ plays a crucial role in the pathogenesis of SSc and raise the possibility of a therapeutic approach with anti-TGFβ antibodies or a TGFβ1 antisense oligonucleotide.