NF-kB inhibitory molecule mediated TNF responsiveness of rheumatoid arthritis delivered fibroblast-like synoviocyte

• Project/Area Number: 25462390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: IGARASHI HIDEYA 川崎医科大学, 医学部, 准教授 (40291538)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節リウマチ / 滑膜線維芽細胞 / NF-kappaB / ABIN-3 / NEDD4L / ユビキチンリガーゼ / アポトーシス / ABIN / ユビキチン / E3ユビキチンリガーゼ / TNFR2 / TNFα / DNAチップ

Outline of Final Research Achievements

To elucidate the molecular mechanisms for the pro-inflammatory effect of ABIN-3, an inhibitor for NF-κB activation, we established the stable transfectant constitutively expressing ABIN-3 by enforced expression in fibroblast-like synoviocyte cell line MH7A derived from rheumatoid arthritis patient designated as A3G. A3G showed the phenotypic changes as spindle-like appearance, growth retardation, decreased expression of MMPs and ALDH1A1, and down-regulated activity of Erk and Akt. We identified E3 ubiquitin ligase NEDD4L as a binding partner of ABIN-3 by mass-spectrometry and enforced expression.

Research Products

• [Journal Article] TNF receptor type 2 transmits caspase-dependent apoptotic signals in fibroblast-like synoviocytes derived from rheumatoid arthritis. (2015)
  • Author(s): Hirano H, Igarashi H, Morita Y, Ishihara K.
  • Journal Title: Kawasaki Medical Journal Volume: 41 Pages: 29-40
  • DOI: 10.11482/KMJ-E41(2)29
  • NAID: 110009986978
  • ISSN: 0385-0234, 2434-3404
  • Peer Reviewed
• [Presentation] NF-κB抑制因子ABIN-3はRA治療の標的分子となりうるか (2015)
  • Author(s): 五十嵐英哉
  • Organizer: 第26回日本リウマチ学会中国・四国支部学術集会シンポジウム リウマチ性疾患の基礎研究
  • Place of Presentation: 岡山
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] 関節リウマチ由来滑膜線維芽細胞において2型TNF受容体（TNFR2）はカスパーゼを介するアポトーシスシグナルを伝達する (2015)
  • Author(s): 平野紘康、五十嵐英哉、矢作綾野、守田吉孝、石原克彦
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-22
• [Presentation] ABIN（A20-Binding Inhibitors of NF-kB）-3は関節リウマチ由来滑膜線維芽細胞（RA-FLS）株でAktのユビキチン化を制御する (2015)
  • Author(s): 五十嵐英哉、石原克彦
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-22
• [Remarks] 関節リウマチ（RA）由来滑膜線維芽細胞の遺伝子異常
  • URL: http://www.kawasaki-m.ac.jp/med/study/info.php?id=208