| Project/Area Number |
15K09525
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Kobe University |
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Principal Investigator |
Saegusa Jun 神戸大学, 医学部附属病院, 講師 (20514970)
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| 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)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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 / グルタミナーゼ１ / グルタミノリシス / 代謝 |
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| 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.
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