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Potential of SPACIA1 as a druggable target of rheumatoid arthritis

Research Project

Project/Area Number 25461490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Fujii Ryoji  聖マリアンナ医科大学, 医学研究科, 講師 (10333535)

Co-Investigator(Renkei-kenkyūsha) YUDO Kazuo  聖マリアンナ医科大学, 医学研究科, 教授 (60272928)
KOMATSU Rie  聖マリアンナ医科大学, 医学研究科, 研究技術員 (80517475)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords関節リウマチ / 滑膜 / 細胞増殖 / 炎症 / 滑膜炎 / リウマチ
Outline of Final Research Achievements

SPACIA1 is a gene associated with abnormal synovial proliferation in rheumatoid arthritis (RA). We previously showed that SPACIA1 transgenic mice exhibited early onset and rapid progression of collagen-induced arthritis (CIA). In the present study, we showed SPACIA1 could be involved in expression of CDK6 gene, a G1 phase-cell cycle factor, via mRNA stability. We also confirmed that TNF-alpha regulates CDK6 expression on transcriptional level in RA-synoviocytes. Unfortunately, even SPACIA1-deficient mice were investigated onset of CIA, therefore we focused CDK6, not SPACIA1, to assess the potential as a druggable target of RA. CDK6 knockdown by its siRNA inhibited the proliferation of RA-synoviocytes. Moreover, treatment of CDK6 inhibitor to mice almost completely prevented development of CIA.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2015 2014 2013

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Mitochondrial Ubiquitin Ligase Activator of NF-κB (MULAN) regulates NF-κB signaling in ER stress-stimulated cells.2016

    • Author(s)
      Fujita H, Aratani S, Fujii R, Yamano Y, Yagishita N, Araya N, Izumi T, Azakami K, Hasegawa D, Nishioka K and Nakajima T
    • Journal Title

      Int J Mol Med.

      Volume: 37 Issue: 6 Pages: 1611-1618

    • DOI

      10.3892/ijmm.2016.2566

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] SPACIA1/SAAL1が制御するCDK6発現量の減少はRA滑膜細胞の増殖を抑制する2017

    • Author(s)
      小松梨恵、遊道和雄、仁木久照、西岡久寿樹、中島利博、藤井亮爾
    • Organizer
      日本リウマチ学会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] SPACIA1/SAAL1の遺伝子欠損はコラーゲン誘導関節炎モデルにおける関節炎の進展を軽減する2016

    • Author(s)
      小松梨恵、關巌、佐藤知雄、青野浩之、山野嘉久、遊道和雄、仁木久照、西岡久寿樹、中島利博、藤井亮爾
    • Organizer
      日本リウマチ学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] SPACIA1/SAAL1-Deficient Mice Show Reduced Disease Progression in Collagen-Induced Arthritis.2015

    • Author(s)
      Ryoji Fujii, Iwao Seki, Rie Komatsu, Miwa Takai, Tomomi Kohara, Tomoo Sato, Kohji Konomi, Hiroyuki Aono, Kazuo Yudoh, Kusuki Nishioka, Toshihiro Nakajima
    • Organizer
      American College of Rheumatology
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-11-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of CDK6 inhibitor on mice collagen-induced arthritis model.2015

    • Author(s)
      Rie Komatsu, Tomoo Sato, Yoshihisa Yamano, Kazuo Yudoh, Moroe Beppu, Kusuki Nishioka, Toshihiro Nakajima, Ryoji Fujii
    • Organizer
      第59回日本リウマチ学会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Functional CDK6 expression controlled by SPACIA1 in RA synoviocite proliferation.2014

    • Author(s)
      Komatsu Rie, Sato Tomoo, Yamano Yoshihisa, Yudoh Kazuo, Beppu Moroe, Nishioka Kusuki Nakajima Toshihiro, Fujii Ryoji
    • Organizer
      日本リウマチ学会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都港区)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis of a transcriptional complex on the core promoter of SPACIA1 gene, which associated with synovitis.2013

    • Author(s)
      藤井亮爾
    • Organizer
      日本リウマチ学会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Research-status Report
  • [Presentation] 滑膜炎関連因子SPACIA1によるCDK6の遺伝子発 現調節機構の解析.2013

    • Author(s)
      小松梨恵
    • Organizer
      日本リウマチ学会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Research-status Report
  • [Presentation] CDK6 Transcripts Expression Control By The Synoviocyte Proliferation Gene, SPACIA1.2013

    • Author(s)
      Rie Komatsu
    • Organizer
      American College of Rheumatology
    • Place of Presentation
      San Diego (USA)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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