Regulation of rheumatoid synovial fibroblasts focusing on layilin-dependent epithelial-mesenchymal transition-like changes
Project/Area Number |
16K09910
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
KATO TOMOHIRO 聖マリアンナ医科大学, 医学部, 教授 (80233807)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 滑膜線維芽細胞 / 関節リウマチ / 上皮間葉移行様変化 / ライリン / 滑膜細胞 / Layilin / 上皮間葉移行 / 上皮間葉 |
Outline of Final Research Achievements |
Firstly, in proteomic analysis, we successfully identified 24 protein spots affected by layilin-silencing in human synovial fibroblasts. As a result, 15 (62.5%) out of the 24 protein spots were assigned to epithelial-mesenchymal transition (EMT)-related proteins. These data suggest that layilin is deeply involved in EMT and EMT-like changes. Secondly, we found that layilin up-regulated the expression of snail family transcriptional repressor 1 (SNAI1) via down-regulation of metastasis-associated protein 3 (MTA3) and that enhanced the cellular invasive ability. Thirdly, using the CRISPR-Cas9 method, we successfully established the first layilin-deficient (homo, LAYN-/-) mice to clarify the physiological and pathogenic roles of layilin. This is expected to be a useful tool for the clarification.
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Academic Significance and Societal Importance of the Research Achievements |
滑膜細胞のEMT様変化自体を研究している論文は数が少なく、これからの分野である。また、ライリンの機能に関しても明らかにされていない点が多い。その中で、RAで高値となるTNF-αがライリンを介して EMTを起こすという独創的な仮説を提唱し、本研究でその実験的根拠を一部見出した点に学術的意義がある。本研究の長期的目標は、滑膜細胞のEMT様変化抑制、それによる異常増殖抑制・骨浸潤抑制によりRAの治療を行うということである。著効はするが高価でかつ易感染性などの副作用のある現在の生物学的製剤とは全く機序の異なる治療が可能となるところが実用上の極めて大きな意義である。
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Report
(4 results)
Research Products
(7 results)