A metabolic approach for discovering therapeutic target in rheumatoid arthritis synovial fibroblast

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09525
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kobe University
• Principal Investigator: Saegusa Jun 神戸大学, 医学部附属病院, 講師 (20514970)
• Co-Investigator(Kenkyū-buntansha): 森信 暁雄 神戸大学, 医学研究科, 准教授 (10294216) ; 河野 誠司 神戸大学, 医学部附属病院, 特命教授 (20351512)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 関節リウマチ / グルタミン代謝 / 滑膜細胞 / 解糖系 / メタボロミクス

Outline of Final Research Achievements

Fibroblast-like synoviocytes from rheumatoid arthritis patients (RA-FLS) exhibit several tumor cell-like characteristics; however, the role of glucose and glutamine metabolism in the aberrant proliferation of these cells is unclear. We evaluated the role of these metabolic pathways in RA-FLS and in mouse model of RA.
GLS1 expression was increased in RA-FLS. RA-FLS proliferation was reduced under glutamine-deprived, but not glucose-deprived, conditions. Cell growth of RA-FLS was inhibited by GLS1 siRNA or GLS1 inhibitor treatment. Treating RA-FLS with either IL-17 or PDGF resulted in increased GLS1 levels. GLS1 inhibitor ameliorated the arthritis and decreased the number of Ki-67-positive synovial cells in SKG mice. Our results suggested that glutamine metabolism is involved in the pathogenesis of RA and that GLS1 plays an important role in regulating RA-FLS proliferation, and may be a novel therapeutic target for RA.

Free Research Field

臨床免疫学