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

Abstract

Transforming growth factor (TGF)-β 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-β in the synovial tissue and synovial fluids of RA patients. In this study, we examined the expression of TGF-β receptors in synovial fibroblasts of patients with RA and demonstrated the significance in functional responses of synovial fibroblasts to TGF-β in this disorder. Transforming growth factor β1 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 β1 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-β 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-β 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-β receptor type II, which is associated with altered responses to TGF-β observed in CTGF expression, chemotaxis, and proliferation of RA synovial fibroblasts, and may have an important role in the pathogenesis of RA.