The functions of the post-translational modifications in rheumatoid arthritis

• Project/Area Number: 22790947
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Tokyo Medical University
• Principal Investigator: ARATANI Satoko 東京医科大学, 医学部, 助教 (40387064)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: リウマチ学 / ユビキチン化 / 関節リウマチ / Synoviolin / シトルリン化 / PADI4 / 転写後修飾

Research Abstract

Rheumatoid Arthritis(RA) is a chronic inflammatory joint disease and characterized by synovial hyperplasia. We previously cloned E3 ubiquitin ligase, Synoviolin, as a regulatory factor of cell proliferation and suggested that endoplasmic reticulum(ER) associated degradation system via Synoviolin has important roles for overgrowth of synoviocytes. Meanwhile, Peptidyl-Arginine Deiminases 4(PADI4) is identified as the RA-susceptible gene. However functions of citrulinated proteins with PADI are unclear. In this study, I hypothesize that the accumulation of citrullinated proteins in RA synoviocytes could associate for ER stress and explore the crosstalk of ubiquitination and citrullination.

Research Products

• [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: (in press)
  • 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: 20 Pages: 40-44
  • NAID: 10030206754
  • 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
• [Journal Article] Overexpression of SPACIA1/SAAL1, a new gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans (2011)
  • Author(s): Sato T, Fujii R, Konomi K, Yagishita N, Aratani S, Araya N, Aono H, Yudoh K, Suzuki N, Beppu M, Yamano Y, Nishioka K, Nakajima T
  • Journal Title: Arthritis Rheum Volume: 63 Pages: 3833-3842
  • Peer Reviewed
• [Journal Article] Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes (2011)
  • Author(s): Sato T, Konomi K, Fujii R, Aono H, Aratani S, Yagishita N, Araya N, Yudoh K, Beppu M, Yamano Y, Nishioka K, Nakajima T
  • Journal Title: Ann Rheum Dis Volume: 70 Pages: 221-226
  • Peer Reviewed
• [Journal Article] Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type1-associated neurological disease (2011)
  • Author(s): Araya N, Takahashi K, Sato T, Nakamura T, Sawa C, Hasegawa D, Ando H, Aratani S, Yagishita N, Fujii R, Oka H, Nishioka, K, Nakajima T, Mori N, Yamano Y
  • Journal Title: Antivir Ther Volume: 16 Pages: 89-98
  • Peer Reviewed
• [Journal Article] Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes (2011)
  • Author(s): 荒谷聡子, 他11名
  • Journal Title: Annals of the Rheumatic Diseases Volume: 70 Pages: 221-226
  • Peer Reviewed
• [Journal Article] Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type1-associated neurological disease (2011)
  • Author(s): 荒谷聡子, 他14名
  • Journal Title: Antiviral Therapy Volume: 16 Pages: 89-98
  • Peer Reviewed
• [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)
  • Peer Reviewed
• [Journal Article] E3 ubiquitin ligase synoviolin is involved in liver fibrogenesis. (2010)
  • Author(s): 荒谷聡子, 他18名
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Presentation] The functions of the post-translational modifications in rheumatoid arthritis (2011)
  • Author(s): Aratani S Yagishita N, Kanazawa T, Nakajima F, Yamano Y, Nishioka K, Nakajima T
  • Organizer: Bio-Rheumatology International Congress(BRIC) Tokyo : The 8th GARN Meeting
  • Place of Presentation: Tokyo, Japan(Hilton Tokyo Bay Hotel)
  • Year and Date: 2011-11-15
• [Presentation] The functions of the post-translational modifications in rheumatoid arthritis (2011)
  • Author(s): 荒谷聡子, 他6名
  • Organizer: 1st Bio-Rheumatology International Congress (BRIC)Tokyo,/The 8th GAEN Meeting
  • Place of Presentation: 東京
  • Year and Date: 2011-11-15
• [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] Importance of E3 ubiquitin ligase Synoviolin in fibrogenesis (2011)
  • Author(s): 八木下尚子、荒谷聡子, 他3名
  • Organizer: American College of Rheumatology the 75th Annual Scientific Meeting
  • Place of Presentation: Cicago
  • Year and Date: 2011-11-08
• [Presentation] 翻訳後タンパク質修飾からみた関節リウマチの病態研究 (2011)
  • Author(s): 荒谷聡子, 他4名
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-07-20
• [Presentation] 翻訳後タンパク質修飾からみた関節リウマチの病態研究 (2011)
  • Author(s): 荒谷聡子、八木下尚子、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
• [Presentation] E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis (2011)
  • Author(s): Aratani S Yagishita N, Hasegawa D, Nishioka K, Nakajima T
  • Organizer: Ubiquitin Drug Discovery and Diagnostics
  • Place of Presentation: Philadelphia, U. S. A.
  • Year and Date: 2011-07-12
• [Presentation] Synoviolin ; a novel regulator for fibrosis (2011)
  • Author(s): Aratani S Yagishita N, Hasegawa D, Nishioka K, Nakajima T
  • Organizer: Ubiquitin Drug Discovery and Diagnostics
  • Place of Presentation: Philadelphia, U. S. A.
  • Year and Date: 2011-07-12
• [Presentation] E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis (2011)
  • Author(s): 荒谷聡子, 他4名
  • Organizer: Ubiquitin Drug Discovery and Diagnostics 2011
  • Place of Presentation: Philadelphia
  • Year and Date: 2011-07-12
• [Remarks]
  • URL: http://www.tokyo-med.ac.jp/rrc/
• [Remarks]
  • URL: http://www.tokyo-med.ac.jp/rrc/
• [Remarks]
  • URL: http://www.tokyo-med.ac.jp/rrc/