The mechanism how RasGRP4 promotes proliferation of synovial fibroblasts in rheumatoid arthritis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Hokkaido University
• Principal Investigator: Yasuda Shinsuke 北海道大学, 医学研究院, 准教授 (00374231)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Keywords: 関節リウマチ / 線維芽細胞様滑膜細胞 / Ras / RasGRP4

Outline of Final Research Achievements

RasGRP4 is a guanine exchange factor for Ras, expressed mainly in mast cells, monocytes and neutrophils. We previously found aberrant RasGRP4 expression in fibriblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) that controls proliferation of FLS (Kono, Yasuda et al Arthritis Rheumatol 2015). Downstream of RasGRP4, Ras, MAPK activation was confirmed. We investigated the possibility of treatment targeting RasGRP4-Ras-MAPK pathway. Tipifarnib is a farnesyltransferase inhibitor that inhibits Ras activation, mostly tested in clinical trials for neoplasms. Treatment with tipifarnib inhibited FLS proliferation in a dose-dependent manner (Shimamura, Yasuda et al, EAGOR meeting 2017). We suggest inhibition of Ras activation as a feasible treatment for RA).

Free Research Field

関節リウマチ・全身性自己免疫疾患