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Inhibitory effects of H-Ras/Raf-1-binding affibody molecules on synovial cell function

Research Project

Project/Area Number 24791013
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionHyogo Medical University

Principal Investigator

SEKIGUCHI Masahiro  兵庫医科大学, 医学部, 助教 (50528958)

Research Collaborator IWASAKI Tsuyoshi  兵庫医療大学, 薬学部, 教授 (10151721)
SANO Hajime  兵庫医科大学, 医学部, 教授 (00196304)
SHIBASAKI Seiji  兵庫医療大学, 共通教育センター, 准教授 (50342530)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords人工抗体 / Affibody
Outline of Final Research Achievements

Affibody molecules targeting H-Ras (Zras122,Zras220, and Zras521) or Raf-1 (Zraf322) were introduced into the MH7A synovial cell line using two delivery methods: transfection with plasmids encoding the affibody molecules or direct introduction of affibody protein using a cell-penetrating peptide reagent. Affibody molecules could inhibit IL-6 and PGE2 production in TNF-α-stimulated MH7A cells. The inhibitory effect was stronger when affibody molecules were delivered as proteins via a cell-penetrating peptide reagent than when plasmid-DNA encoding the affibody moelcules was transfected into the cells. Plasmid-expressed Zras220 inhibited phosphorylation of ERK in TNF-α-stimulated MH7A cells. Protein-introduced Zraf322 inhibited the production of IL-6 and PGE2 and inhibited cell proliferation in MH7A cells. Affibody molecules specific for H-Ras and Raf-1 can affect intracellular signal transduction and inhibit cell proliferation and production of inflammatory mediators by synovial cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (4 results)

All 2014 2013 2012

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results)

  • [Journal Article] Inhibitory effects of H-Ras/Raf-1-binding affibody molecules on synovial cell function2014

    • Author(s)
      Seiji Shibasaki
    • Journal Title

      AMB Express

      Volume: 4:82 Issue: 1 Pages: 1-9

    • DOI

      10.1186/s13568-014-0082-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 人工抗体Affibodyによる炎症性メディエーター産生の制御2014

    • Author(s)
      芝崎 誠司、関口 昌弘、北野 幸恵、岩崎 剛、佐野 統
    • Organizer
      第58回日本リウマチ学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗Ras人工抗体Affibodyの取得と細胞内シグナル伝達経路の阻害2013

    • Author(s)
      臼井千裕
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] 滑膜細胞における分子標的薬ならびに人工抗体リガンドを用いたサイトカイン抑制効果2012

    • Author(s)
      渡邊沙知子
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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