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
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) |