The transcriptional regulation of Synoviolin in rheumatoid synovial cells.

2011 Fiscal Year Final Research Report

• Project/Area Number: 20689019
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: YAGISHITA Naoko 聖マリアンナ医科大学, 医学(系)研究科(研究院), 講師 (40367389)
• Project Period (FY): 2008 – 2011
• Keywords: 関節リウマチ / 滑膜細胞 / 滑膜細胞増殖 / シノビオリン / 小胞体関連分解E3ユビキチンリガーゼ / シノビオリンプロモーター

Research Abstract

Rheumatoid arthritis(RA) significantly affects quality of life. We recently cloned synoviolin, a RING-typeE3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation(ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. In this study, we found that ILF-3 up-regulates synoviolin expression with GABPα in rheumatoid synovial cells. Moreover, we demonstrated that Synoviolin is involved in not only onset of RA but also development of liver fibrosis. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We recently identified two classes of small molecules which inhibited synoviolin activity. These inhibitors suppressed the proliferation of rheumatoid synovial cells, and significantly reduced the severity of disease in a mouse model of RA. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of RA.

Research Products

• [Journal Article] E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis (2010)
  • Author(s): Hasegawa D, Fujii R, Yagishita N, Matsumoto N, Aratani S, Izumi T, Azakami K, Nakazawa M, Fujita H, Sato T, Araya N, Koike J, Tadokoro M, Suzuki N, Nagata K, Senoo H, Friedman SL, Nishioka K, Yamano Y, Itoh F, Nakajima T
  • Journal Title: PLoS One Volume: 5(10) Pages: e13590
  • Peer Reviewed
• [Journal Article] Activation of Synoviolin Promoter in Rheumatoid Synovial Cells by a Novel Transcription Complex of Interleukin Enhancer Binding Factor 3 and GA Binding Protein (2009)
  • Author(s): Izumi T, Fujii R, Izumi T, Nakazawa M, Yagishita N, Tsuchimochi K, Yamano Y, Sato T, Fujita H, Aratani S, Araya N, Azakami K, Hasegawa D, Kasaoka S, Tsuruta R, Yokouti M, jiri K, Beppu M, Maruyama I, Nishioka K, Maekawa T, Komiya S, Nakajima T
  • Journal Title: Arthritis Rhe Volume: 60(1) Pages: 63-72
  • Peer Reviewed
• [Presentation] Importance of E3 ubiquitin ligase Synoviolin in fibrogenesis. Bio-Rheumatology International Congress(BRIC) Tokyo (2011)
  • Author(s): Yagishita N, Hasegawa D, Aratani S, Yamano Y, Nakajima T
  • Organizer: The 8th GARN Meeting
  • Place of Presentation: Tokyo, Japan.(Hilton Tokyo Bay Hotel)
  • Year and Date: 2011-11-15
• [Presentation] ER stress signaling as a chronic inflammation (2011)
  • Author(s): Yagishita N, Aratani S, Yamano Y, Nishioka K, Nakajima T
  • Organizer: 2nd Tokyo-Shanghai Workshop on Rheumatology 2011
  • Place of Presentation: Tokyo, Japan.(Hilton Tokyo Bay Hotel)
  • Year and Date: 2011-11-13
• [Presentation] Importance of E3 ubiquitin ligase Synoviolin in fibrogenesis (2011)
  • Author(s): Yagishita N, Hasegawa D, Aratani S, Yamano Y, Nakajima T
  • Organizer: The 2011 ACR/ARHP Annual Scientific Meeting
  • Place of Presentation: Chicago, U. S. A
  • Year and Date: 2011-11-08
• [Presentation] シノビオリンから見た関節リウマチの病態研究 (2011)
  • Author(s): 八木下尚子、中島利博
  • Organizer: 第55回日本リウマチ学会カレントシンポジウム「若手研究者が語るリウマチ性疾患の病態とシグナル伝達」
  • Place of Presentation: 神戸(神戸ポートピアホテル神戸国際会議場神戸国際展示場)
  • Year and Date: 2011-07-18
• [Presentation] E3ユビキチンリガーゼシノビオリンの線維化への関与 (2011)
  • Author(s): 八木下尚子、荒谷聡子、佐藤知雄、藤井亮爾、山野嘉久、西岡久寿樹、中島利博
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸(神戸ポートピアホテル神戸国際会議場神戸国際展示場)
  • Year and Date: 2011-07-18
• [Remarks]
  • URL: http://nanchiken.jp/