2009 Fiscal Year Final Research Report
Implication of Synoviolin in the Pathogenesis of Rheumatoid Arthritis and Liver Fibrosis
| Project/Area Number |
20249052
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Tokyo Medical University (2009-2011)
Choju Medical Institute, Fukushimura Hospital. (2008) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMANO Yoshihisa 聖マリアンナ医科大学, 難病治療研究センター, 准教授 (80445882)
YAGISHITA Naoko 聖マリアンナ医科大学, 難病治療研究センター, 講師 (40367389)
KAMI Masahiro 東京大学, 医科学研究所, 特任教授 (50422423)
HIGUCHI Ituro 鹿児島大学, 大学院・医歯学総合研究科, 准教授 (80183573)
AKATSU Hiroyasu 医療法人さわらび会福祉村病院, 長寿医学研究所, 副所長 (00399734)
KAWAHARA Koichi 大阪工業大学, 工学部, 教授 (10381170)
MARUYAMA Ikuro 鹿児島大学, 大学院・医歯学総合研究科, 教授 (20082282)
OKADA Hidechika 医療法人さわらび会福祉村病院, 長寿医学研究所, 研究員 (30160683)
ARATANI Satoko 東京医科大学, 医学部, 助教 (40387064)
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| Project Period (FY) |
2008 – 2011
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| Keywords | 関節リウマチ / 線維化 / 小胞体関連分解 / 滑膜細胞 / シノビオリン / コンディショナルノックアウトマウス / 化合物 |
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| Research Abstract |
Rheumatoid arthritis(RA) significantly affects quality of life. We recently cloned synoviolin, a RING-typeE3 ubiquitin ligase implicated in the endoplasmic reticulum associated degradation(ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We conducted a high-throughput screen of small molecules to find inhibitors of synoviolin autoubiquitination activity. We identified two classes of small molecules, which inhibited synoviolin activity. Moreover, these inhibitors suppressed the proliferation of rheumatoid synovial cells and significantly reduced the severity of disease in a mouse model of RA. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of RA.
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