The study of physiological mechanisms of rheumatoid synovial cells by Synoviolin
| Project/Area Number |
17K08675
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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 |
Pathological medical chemistry
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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, 医学研究科, 講師 (40367389)
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| Co-Investigator(Kenkyū-buntansha) |
中島 利博 東京医科大学, 医学部, 教授 (90260752)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 関節リウマチ / 滑膜細胞 / シノビオリン / 小胞体関連分解 / E3ユビキチン化酵素 / がん細胞 / エネルギー代謝 |
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| Outline of Final Research Achievements |
We recently cloned Synoviolin as an overexpressing molecule in rheumatoid synovium, and has been verifying its critical roles in RA. Synoviolin is endoplasmic reticulum (ER)-resident E3 ubiquitin ligases, and is involved in ER-associated degradation (ERAD). In addition, Synoviolin negatively regulates the tumor suppressor p53 in the cytoplasm by ubiquitinating p53. Therefore, Synoviolin regulates both apoptosis in response to ER stress and a p53-dependent apoptotic pathway. Furthermore, Synoviolin interacted with and ubiquitinated the thermogenic coactivator peroxisome proliferator activated receptor coactivator (PGC)-1β. Then, Synoviolin regulates mitochondrial biogenesis through negative regulation of PGC-1β. In this study, we investigated the role of synovial cells using synoviolin conditional knockout mice.
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| Academic Significance and Societal Importance of the Research Achievements |
シノビオリンKOマウスは、600以上も存在するといわれるRING型のE3ユビキチン化酵素の中で唯一致死となるマウスであり、時期特異的KOマウスも致死となるという結果をあわせると、シノビオリンは代替性のない分子であり、生体内において非常に重要な機能を持つといえる。また、シノビオリンの酵素活性阻害剤も有することから、ある1つの機能が明らかとなればその活用範囲は大きい。シノビオリンはRA、がん、そして慢性炎症、線維化と多くの病態に関与することが考えられるため、RA領域にとどまらない大きな広がりをもった意義ある研究になると考えている。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] The NRF2-PGC-1β pathway activates kynurenine aminotransferase 4 via attenuation of an E3 ubiquitin ligase, Synoviolin, in a cecal ligation/perforation -induced septic mouse model.2018
Author(s)
Ishida Y, Fujita H, Aratani S, Chijiiwa M, Taniguchi N, Yokota M, Ogihara Y, Uoshima N, Nagashima F, Uchino H, Nakajima T.
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Journal Title
Mol. Med. Rep.
Volume: 18(2)
Pages: 2467-2475
Related Report
Peer Reviewed / Open Access
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[Journal Article] An E3 Ubiquitin Ligase, Synoviolin, Is Involved in the Degradation of Homocysteine-Inducible Endoplasmic Reticulum Protein.2018
Author(s)
Maeda T, Fujita Y, Tanabe-Fujimura C, Zou K, Liu J, Liu S, Kikuchi K, Shen X, Nakajima T, Komano H.
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Journal Title
Biol. Pharm. Bull.
Volume: 41(6)
Pages: 915-919
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoidarthritis: a randomised placebocontrolledphase IV study.2018
Author(s)
Matsubara T, Inoue H,Nakajima T, Tanimura K, Sagawa A, Sato Y, Osano K, Nagano S, Ueki Y, Hanyu T, Hashizume K, Amano N, Tanaka Y, Takeuchi T.
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Journal Title
Related Report
Peer Reviewed / Open Access
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