Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts 英文参考文献.docVIP

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Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts 英文参考文献.doc

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Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts 英文参考文献

Available online /content/7/3/R476 Research article Open Access Vol 7 No 3 Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts Shingo Nakayamada1, Hitoshi Kurose2, Kazuyoshi Saito1, Akira Mogami3 and Yoshiya Tanaka1 1First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Fukuoka, Japan 2Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan 3Pharmaceuticals Research Unit, Research Development Division, Mitsubishi Pharma Corporation, Yokohama, Japan Corresponding author: Yoshiya Tanaka, tanaka@med.uoeh-u.ac.jp Received: 11 Nov 2004 Revisions requested: 24 Nov 2004 Revisions received: 10 Jan 2005 Accepted: 18 Jan 2005 Published: 18 Feb 2005 Arthritis Research Therapy 2005, 7:R476-R484 (DOI 10.1186/ar1694) ? 2005 Nakayamada et al.; licensee BioMed Central Ltd. /content/7/3/R476 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Rho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. We studied its roles in synovial fibroblasts (SFs) in patients with rheumatoid arthritis (RA) and clarified its relevance to RA synovitis, with the following results. 1)We found that the thrombin receptor was overexpressed on RA synovial fibroblasts (RA SFs) and that thrombin induced a marked proliferation and progression of the cell cycle to the S phase in these cells. 2)We also found that thrombin efficiently activated Rho. 3)Rho activation and proliferation and the progression of the cell cycle