| Project/Area Number |
23659502
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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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 | St. Marianna University School of Medicine |
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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)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 関節リウマチ / 滑膜細菌 / シノビオリン / 小胞体関連分解 / 線維化 / 阻害剤 / 滑膜細胞 |
|---|
| Research Abstract |
Rheumatoid arthritis (RA) significantly affects quality of life. We recently cloned synoviolin, an E3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation pathway. Synoviolin is highly expressed in rheumatoid synovial cells and is involved in the pathogenesis of RA. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We recently identified two classes of small molecules, named LS-101 and LS-102, which inhibited synoviolin activity. LS-102 selectively inhibited synoviolin enzymatic activity, while LS-101 inhibited a broad array of RING-type E3 ligases. Moreover, these inhibitors suppressed the proliferation of rheumatoid synovial cells, and significantly reduced the severity of disease in a mouse model of RA and liver fibrosis. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of fibrosis.
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