The transcriptional regulation of Synoviolin in rheumatoid synovial cells.
Project/Area Number |
20689019
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
膠原病・アレルギー・感染症内科学
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Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
YAGISHITA Naoko 聖マリアンナ医科大学, 医学(系)研究科(研究院), 講師 (40367389)
|
Project Period (FY) |
2008 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2010: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2009: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2008: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
|
Keywords | 関節リウマチ / 滑膜細胞 / 滑膜細胞増殖 / シノビオリン / 小胞体関連分解E3ユビキチンリガーゼ / シノビオリンプロモーター / 小胞体関連分解 / E3ユビキチンリガーゼ / 自己免疫疾患 / Ets binding site |
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. In this study, we found that ILF-3 up-regulates synoviolin expression with GABPα in rheumatoid synovial cells. Moreover, we demonstrated that Synoviolin is involved in not only onset of RA but also development of liver fibrosis. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We recently identified two classes of small molecules which inhibited synoviolin activity. 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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Report
(4 results)
Research Products
(14 results)
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[Journal Article] E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis2010
Author(s)
Hasegawa D, Fujii R, Yagishita N, Matsumoto N, Aratani S, Izumi T, Azakami K, Nakazawa M, Fujita H, Sato T, Araya N, Koike J, Tadokoro M, Suzuki N, Nagata K, Senoo H, Friedman SL, Nishioka K, Yamano Y, Itoh F, Nakajima T
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Activation of Synoviolin Promoter in Rheumatoid Synovial Cells by a Novel Transcription Complex of Interleukin Enhancer Binding Factor 3 and GA Binding Protein2009
Author(s)
Izumi T, Fujii R, Izumi T, Nakazawa M, Yagishita N, Tsuchimochi K, Yamano Y, Sato T, Fujita H, Aratani S, Araya N, Azakami K, Hasegawa D, Kasaoka S, Tsuruta R, Yokouti M, jiri K, Beppu M, Maruyama I, Nishioka K, Maekawa T, Komiya S, Nakajima T
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Journal Title
Arthritis Rhe
Volume: 60(1)
Pages: 63-72
Related Report
Peer Reviewed
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