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 (3)H-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-1 beta (IL-1 beta), tumor necrosis factor alpha, and transforming growth factor beta 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-1 beta. CONCLUSION: These results suggest that activin A acts as a growth factor of FLS in RA.
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 RApatients 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 (3)H-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-1 beta (IL-1 beta), tumor necrosis factor alpha, and transforming growth factor beta 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-1 beta. CONCLUSION: These results suggest that activin A acts as a growth factor of FLS in RA.
Authors: Hatem A Elshabrawy; Michael V Volin; Abdul B Essani; Zhenlong Chen; Iain B McInnes; Katrien Van Raemdonck; Karol Palasiewicz; Shiva Arami; Mark Gonzalez; Hossam M Ashour; Seung-Jae Kim; Guofei Zhou; David A Fox; Shiva Shahrara Journal: Angiogenesis Date: 2018-01-11 Impact factor: 9.596
Authors: Farida Djouad; Wesley M Jackson; Brent E Bobick; Sasa Janjanin; Yingjie Song; George T J Huang; Rocky S Tuan Journal: Stem Cell Res Ther Date: 2010-05-04 Impact factor: 6.832
Authors: Maria Semitekolou; Themis Alissafi; Maria Aggelakopoulou; Evangelia Kourepini; Harsha H Kariyawasam; Antony B Kay; Douglas S Robinson; Clare M Lloyd; Vily Panoutsakopoulou; Georgina Xanthou Journal: J Exp Med Date: 2009-07-20 Impact factor: 14.307