Relationship of post-translational modifications in RA synoviocytes

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥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.

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) Issue: 5 Pages: 846-850
  • DOI: 10.1007/s10165-012-0759-x
  • NAID: 10031201138
  • 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, Itoh K, Yamano Y, Nakamura H, Asukai N, Nakajima T, Nishioka K
  • Journal Title: Arthritis Research & Therapy Volume: 15(5) Issue: 5 Pages: R130-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. and Nakajima T
  • Journal Title: Int. J. Mol. Med Volume: 30 Issue: 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): 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
  • 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
• [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)
• [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
• [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: Four Seasons Hotel Philadelphia, USA
• [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
• [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)
• [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
• [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: 4th Annual Ubiquitin Drug Discovery & Diagnostics Conference 2012
  • Place of Presentation: Four Seasons Hotel Philadelphia, USA
• [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
• [Remarks]
• [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
• [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
• [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
• [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
• [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