Activin A induces cell proliferation of fibroblast-like synoviocytes in rheumatoid arthritis
Akito Maeshima
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorShin Yamashita
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorHidekazu Ikeuchi
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorYoriaki Kaneko
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorTakashi Kuroiwa
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorKeiju Hiromura
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorKazue Ueki
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorItaru Kojima
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
Search for more papers by this authorCorresponding Author
Yoshihisa Nojima
Gunma University School of Medicine, Maebashi, Japan
Third Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, JapanSearch for more papers by this authorAkito Maeshima
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorShin Yamashita
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorHidekazu Ikeuchi
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorYoriaki Kaneko
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorTakashi Kuroiwa
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorKeiju Hiromura
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorKazue Ueki
Gunma University School of Medicine, Maebashi, Japan
Search for more papers by this authorItaru Kojima
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
Search for more papers by this authorCorresponding Author
Yoshihisa Nojima
Gunma University School of Medicine, Maebashi, Japan
Third Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, JapanSearch for more papers by this authorAbstract
Objective
To investigate the expression of activin A and its receptors in rheumatoid arthritis (RA) synovial tissues, and to determine the effect of activin A on cultured fibroblast-like synoviocytes (FLS).
Methods
The localization of activin A and activin type II receptor (ARII) in synovial tissues of RA patients was analyzed by immunohistochemistry. The expression of activin A and activin receptors in human cultured FLS was examined by reverse transcriptase–polymerase chain reaction and Western blotting. Enzyme-linked immunosorbent assay was used to measure activin A in culture supernatants. The cell growth of FLS was determined by 3H-thymidine incorporation and MTT assay.
Results
Immunohistochemical analysis confirmed the up-regulation of activin A in rheumatoid synovium as compared with osteoarthritis or normal joint tissues. CD68+ macrophage-lineage cells and vimentin-positive FLS were identified as activin-producing cells in rheumatoid synovium. Both cell types also expressed ARII. The expression of activin A and ARII on cultured FLS was confirmed at the protein and messenger RNA levels. Interleukin-1β (IL-1β), tumor necrosis factor α, and transforming growth factor β activated FLS to secrete activin A. Recombinant activin A accelerated the proliferation of FLS, while follistatin, an endogenous activin antagonist, partially inhibited FLS proliferation induced by IL-1β.
Conclusion
These results suggest that activin A acts as a growth factor of FLS in RA.
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