OBJECTIVE: To delineate the expression of transforming growth factor beta-inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like synoviocytes (FLS). METHODS: Synovial tissue was obtained from patients with rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated using enzymatic treatment. Immunohistochemical staining was performed to show the expression of betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-H3 from FLS was determined by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell adhesion and migration assays were performed using the YH18 peptide in the fourth fas-1 domain of betaIG-H3 and function-blocking antibodies to integrins. RESULTS: Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced betaIG-H3, which was up-regulated by transforming growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration of FLS through interaction with alpha v beta3 integrin. Cytokines failed to affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited adhesion and migration in a dose-dependent manner. CONCLUSION: The results suggest that betaIG-H3, which is abundantly expressed in RA synovial tissue, plays a regulatory role in chronic destructive inflammation through the modulation of the adhesion and migration of FLS. This finding indicates the relevance of betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential therapeutic targets in this disease.
OBJECTIVE: To delineate the expression of transforming growth factor beta-inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like synoviocytes (FLS). METHODS: Synovial tissue was obtained from patients with rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated using enzymatic treatment. Immunohistochemical staining was performed to show the expression of betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-H3 from FLS was determined by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell adhesion and migration assays were performed using the YH18 peptide in the fourth fas-1 domain of betaIG-H3 and function-blocking antibodies to integrins. RESULTS: Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced betaIG-H3, which was up-regulated by transforming growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration of FLS through interaction with alpha v beta3 integrin. Cytokines failed to affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited adhesion and migration in a dose-dependent manner. CONCLUSION: The results suggest that betaIG-H3, which is abundantly expressed in RA synovial tissue, plays a regulatory role in chronic destructive inflammation through the modulation of the adhesion and migration of FLS. This finding indicates the relevance of betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential therapeutic targets in this disease.
Authors: Rogelio Zamilpa; Rajesha Rupaimoole; Clyde F Phelix; Maria Somaraki-Cormier; William Haskins; Reto Asmis; Richard G LeBaron Journal: Matrix Biol Date: 2009-06-06 Impact factor: 11.583
Authors: Lilian Shelton; David Troilo; Megan R Lerner; Yuriy Gusev; Daniel J Brackett; Jody Summers Rada Journal: Mol Vis Date: 2008-08-11 Impact factor: 2.367
Authors: Eon Jeong Nam; Jin Hee Kang; Keum Hee Sa; Shijin Sung; Jae Yong Park; Dong-Gyu Jo; Jae Hyung Park; In San Kim; Young Mo Kang Journal: PLoS One Date: 2016-10-14 Impact factor: 3.240