Relationship of post-translational modifications in RA synoviocytes

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791006
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Tokyo 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
• 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

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.

Research Products

• [Journal Article] The Japanese version of the modified ACR Preliminary Diagnostic Criteria for Fibromyalgia and the Fibromyalgia Symptom Scale : reliability and validity (2013)
  • 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) Pages: 846-850
  • DOI: 10.1007/s10165-012-0759-x
  • Peer Reviewed
• [Journal Article] Vulnerability to traumatic stress in fibromyalgia patients : 19 months follow-up after the Great East Japan Disaster (2013)
  • Author(s): Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, T, Ito K, Yamano Y, Nakamura H, Asukai N, Nakajima T, Nishioka K and Okamura S
  • Journal Title: Arthritis Research & Therapy Volume: 15 Pages: R130
  • DOI: 10.1186/ar4310
  • 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, Nakajima T
  • Journal Title: Int J Mol Med Volume: 30(6) Pages: 1281-1286
  • DOI: 10.3892/ijmm.2012.1129
  • 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 validity (2012)
  • Author(s): Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Kanazawa T, Ito K, Yamano Y, Nakamura H, Nakajima T, Nishioka K
  • Journal Title: Mod Rheumatol Volume: 22(1) Pages: 40-4
  • DOI: 10.1007/s10165-011-0462-3
  • Peer Reviewed
• [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)
  • Year and Date: 20131005-06
• [Presentation] Synoviolin inhibitors have anti-obesity activity (2013)
  • 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
  • Year and Date: 20130723-24
• [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
• [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)
  • Year and Date: 20120915-16
• [Presentation] What tells us from Post-neonatal knock out of synoviolin (2012)
  • 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
  • Year and Date: 20120723-25
• [Remarks]
  • URL: http://www.tokyo-med-ims.com/組織/運動器科学研究部門/
• [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: 特願2013-121694
  • Filing Date: 2013-06-10
• [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: 特願2013-060584
  • Filing Date: 2013-03-22
• [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
  • Industrial Property Number: 特許, 2012-283-763
  • Filing Date: 2012-12-26