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MODERN RHEUMATOLOGY Vol.15 No.2

Vol.15 No.2 に戻る


Transforming growth factor beta stimulates rheumatoid synovial fibroblasts via the type II receptor

Yanjmaa Bira1, Kenji Tani1, Yasuhiko Nishioka1, Junya Miyata1, Keiko Sato1, Akihito Hayashi1, Yutaka Nakaya2 and Saburo Sone1

(1) Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima770-8503, Japan
(2) Department of Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

Received: 29 September 2004 Accepted: 27 December 2004

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Abstract Transforming growth factor (TGF)-beta regulates the function of fibroblasts, and has been shown to have a role in the pathogenesis of rheumatoid arthritis (RA) because several studies have demonstrated the presence of TGF-beta in the synovial tissue and synovial fluids of RA patients. In this study, we examined the expression of TGF-beta receptors in synovial fibroblasts of patients with RA and demonstrated the significance in functional responses of synovial fibroblasts to TGF-beta in this disorder. Transforming growth factor beta 1 stimulated the expression of connective tissue growth factor (CTGF) in fibroblasts of patients with RA more than in those of patients with osteoarthritis (OA). Transforming growth factor beta 1 induced the chemotactic migration of RA synovial fibroblasts and inhibited their proliferation significantly more than OA synovial fibroblasts. Both RA and OA synovial fibroblasts expressed detectable amounts of TGF-beta receptor type II mRNA, but the expression was higher in RA patients than in OA patients, as assessed by reverse transcriptase polymerase chain reaction. There was no significant difference in the expression of TGF-beta receptor type I or type III in synovial fibroblasts between RA and OA patients. These results indicate that synovial fibroblasts of RA patients express the increased TGF-betareceptor type II, which is associated with altered responses to TGF-beta observed in CTGF expression, chemotaxis, and proliferation of RA synovial fibroblasts, and may have an important role in the pathogenesis of RA.

Key words Chemotaxis - Connective tissue growth factor (CTGF) - Fibroblast - Rheumatoid arthritis (RA)-Transforming growth factor beta (TGF-beta)

 
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