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Relationship of post-translational modifications in RA synoviocytes

Research Project

Project/Area Number 24791006
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionTokyo Medical University

Principal Investigator

SATOKO Aratani  東京医科大学, 医学部, 助教 (40387064)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords関節リウマチ / Synoviolin / ユビキチン化 / シトルリン化 / 転写後修飾 / PADI4 / シノビオリン
Research Abstract

We previously cloned E3 ubiquitin ligase, Synoviolin, as a regulatory factor of synoviocytes proliferation in rheumatoid arthritis (RA) and suggested that endoplasmic reticulum (ER) associated degradation system via Synoviolin has important roles for overgrowth of synoviocytes. It is known that the citrullination of proteins is activated in RA and Peptidyl-Arginine Deiminases 4 (PADI4) is identified as the RA-susceptible gene. In regard to these post-trasnslational modifications, we revealed that they associate and citrullination could decrease the ubiquitination by synoviolin and ER stress. In this study, I established synoviolin conditional knockout mice and enzymatic inhibitors of synoviolin and explored the function of post-translational modifications in vivo.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (9 results) Remarks (1 results) Patent(Industrial Property Rights) (5 results)

  • [Journal Article] The Japanese version of the modified ACR preliminary diagnostic criteria for fibromyalgia and the fibromyalgia symptom scale : reliability and validity2013

    • Author(s)
      Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Kanazawa T, Itoh K, Yamano Y, Nakamura H, Nakajima T, Nishioka K
    • Journal Title

      Mod Rheumatol

      Volume: 23(5) Issue: 5 Pages: 846-850

    • DOI

      10.1007/s10165-012-0759-x

    • NAID

      10031201138

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vulnerability to traumatic stress in fibromyalgia patients : 19 months follow-up after the Great East Japan Disaster2013

    • Author(s)
      Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Itoh K, Yamano Y, Nakamura H, Asukai N, Nakajima T, Nishioka K
    • Journal Title

      Arthritis Research & Therapy

      Volume: 15(5) Issue: 5

    • DOI

      10.1186/ar4310

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis.2012

    • Author(s)
      Yagishita N., Aratani S., Leach C., Amano T., Yamano Y., Nakatani K., Nishioka K. and Nakajima T
    • Journal Title

      Int. J. Mol. Med

      Volume: 30 Issue: 6 Pages: 1281-1286

    • DOI

      10.3892/ijmm.2012.1129

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and the Fibromyalgia Symptom Scale : reliability and validity2012

    • Author(s)
      臼井千恵、中島利博, 他9名
    • Journal Title

      Mod.Rheumatol.

      Volume: 20 Issue: 1 Pages: 40-44

    • DOI

      10.1007/s10165-011-0462-3

    • NAID

      10030206754

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] リウマチと肥満を標的としたシノビオリン阻害剤の創薬開発研究の展開2013

    • Author(s)
      荒谷聡子, 藤田英俊, 八木下尚子, 西岡久寿樹, 中島利博
    • Organizer
      第3回医薬工3大学包括連携推進シンポジウム
    • Place of Presentation
      東京薬科大学
    • Year and Date
      2013-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      荒谷聡子, 臼井千恵, 山野嘉久, 西岡健弥, 藤田英俊, 八木下尚子), 伊藤健司, 長田賢一, 中村郁朗, 西岡久寿樹, 中島利博
    • Organizer
      日本線維筋痛症学会 第5回学術集会
    • Place of Presentation
      横浜 (横浜開港記念館)
    • Related Report
      2013 Final Research Report
  • [Presentation] Synoviolin inhibitors have anti-obesity activity2013

    • Author(s)
      Aratani S, Fujita H, Yagishita N, Nishioka K, Nakajima T
    • Organizer
      Ubiquitin Drug Discovery and Diagnostics 2013
    • Place of Presentation
      Philadelphia, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Synoviolin inhibitors have anti-obesity activity2013

    • Author(s)
      Aratani S, Fujita H, Yagishita N, Nishioka K, Nakajima T
    • Organizer
      Ubiquitin Drug Discovery and Diagnostics 2013
    • Place of Presentation
      Four Seasons Hotel Philadelphia, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗疼痛薬による肥満と小胞体ストレスの関与2013

    • Author(s)
      荒谷聡子、臼井千恵、山野嘉久、西岡健弥、藤田英俊、八木下尚子)、伊藤健司、長田賢一、中村郁朗、西岡久寿樹、中島利博
    • Organizer
      日本線維筋痛症学会 第 5 回学術集会
    • Place of Presentation
      横浜開港記念館
    • Related Report
      2013 Annual Research Report
  • [Presentation] 線維筋痛症における疼痛シグナル解析モデルの構築2012

    • Author(s)
      荒谷聡子, 臼井千恵, 八木下尚子, 西岡健弥, 山野嘉久, 藤田英俊, 伊藤健司, 長田賢一, 中村郁朗, 岡寛, 西岡久寿樹, 中島利博
    • Organizer
      日本線維筋痛症学会 第4回学術集会
    • Place of Presentation
      長崎 (長崎ブリックホール)
    • Related Report
      2013 Final Research Report
  • [Presentation] What tells us from Post-neonatal knock out of synoviolin2012

    • Author(s)
      Nakajima T, Yagishita N, Aratani S, Fujita H, Nishioka K
    • Organizer
      Ubiquitin Drug Discovery and Diagnostics 2012
    • Place of Presentation
      Philadelphia, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] What tells us from Post-neonatal knock out of synoviolin2012

    • Author(s)
      Nakajima T, Yagishita N, Aratani S, Fujita H, Nishioka K
    • Organizer
      4th Annual Ubiquitin Drug Discovery & Diagnostics Conference 2012
    • Place of Presentation
      Four Seasons Hotel Philadelphia, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] リウマチと肥満を標的としたシノビオリン阻害剤の創薬開発研究の展開

    • Author(s)
      荒谷聡子、藤田英俊、八木下尚子、西岡久寿樹、中島利博
    • Organizer
      第3 回医薬工 3 大学包括連携推進シンポジウム
    • Place of Presentation
      東京薬科大学
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 小胞体ストレスシグナルを抑制することによる, 薬剤の副作用としての体重増加や肥満を防止するために用いられる肥満防止剤2013

    • Inventor(s)
      中島利博, 荒谷聡子, 臼井千恵, 山野嘉久, 西岡健弥, 藤田英俊, 八木下尚子, 伊藤健司, 中村郁朗, 西岡久寿樹
    • Industrial Property Rights Holder
      株式会社エム・エス・エス
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-121694
    • Filing Date
      2013-06-10
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] IL-2 産生抑制2013

    • Inventor(s)
      中島利博, 荒谷聡子, 青野浩之, 西岡久寿樹
    • Industrial Property Rights Holder
      参天製薬株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-060584
    • Filing Date
      2013-03-22
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 小胞体ストレスシグナルを抑制することによる,薬剤の副作用としての体重増加や肥満を防止するために用いられる肥満防止剤2013

    • Inventor(s)
      中島利博、荒谷聡子 他
    • Industrial Property Rights Holder
      株式会社エム・エス・エス
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-121694
    • Filing Date
      2013-06-10
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 1, 3, 5-トリアジン誘導体を有する線維化予防又は治療剤2012

    • Inventor(s)
      中島 利博, 瀬戸口 靖弘, 中島 若巳, 荒谷 聡子, 藤田 英俊
    • Industrial Property Rights Holder
      学校法人東京医科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-12-26
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 1,3,5-トリアジン誘導体を有する線維化予防又は治療剤2012

    • Inventor(s)
      中島利博、瀬戸口靖弘、中島若巳、荒谷聡子、藤田英俊
    • Industrial Property Rights Holder
      中島利博、瀬戸口靖弘、中島若巳、荒谷聡子、藤田英俊
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-12-26
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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