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Analysis of regulatory mechanism for platelet integrin activation kinetics

Research Project

Project/Area Number 18K08327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionOsaka University

Principal Investigator

Hisashi Kato  大阪大学, 医学系研究科, 助教 (20705214)

Co-Investigator(Kenkyū-buntansha) 柏木 浩和  大阪大学, 医学系研究科, 講師 (10432535)
冨山 佳昭  大阪大学, 医学部附属病院, 特任教授(常勤) (80252667)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血小板 / 動脈血栓症 / インテグリン / 血栓症 / 血小板機能異常症 / 血栓 / 血栓・止血
Outline of Final Research Achievements

In this study, we determined the altered phosphorylation status of molecules in platelets from congenital bleeding disorders by mass spectrometry and identified molecules possibly important for platelet integrin activation. Also, the analyses of transgenic mice which express constitutively activated integrin αIIbβ3 (αIIb-R995W) found the association of αIIbβ3 activation with reduced αIIbβ3 expression and impaired platelet function. Platelets of ITP patients were determined by novel flow cytometry-based aggregation assay and found the impaired platelet function in ITP patients.

Academic Significance and Societal Importance of the Research Achievements

本研究は止血のみでなく脳卒中や心筋梗塞など動脈血栓症の発症に重要な血小板活性化機構の解明をめざしたものである。我々のこれまでに行ってきた検討より、血小板機能にとって最も重要なフィブリノゲン受容体インテグリンαIIbβ3が「速やか」かつ「持続的」に活性化することが生体内で重要なことを示してきた。核を持たない血小板は実験上の制約が大きく、血小板機能制御の詳細は明らかにされていない。しかし本研究の着眼点、および先天性血小板機能異常症の症例血小板への質量分析を応用した網羅的解析により得られた知見は、今後の新規抗血小板薬開発へと結びつく可能性があり、大きな社会的意義を持つものであると考えている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Reevaluation of platelet function in chronic immune thrombocytopenia: impacts of platelet size, platelet-associated anti-αIIbβ3 antibodies and thrombopoietin receptor agonists2020

    • Author(s)
      Nishiura N, Kashiwagi H, Akuta K, Hayashi S, Kato H, Kanakura Y, Tomiyama Y.
    • Journal Title

      Br J Haematol .

      Volume: 189 Issue: 4 Pages: 760-771

    • DOI

      10.1111/bjh.16439

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A unique phenotype of acquired Glanzmann thrombasthenia due to non-function-blocking anti-αIIbβ3 autoantibodies2018

    • Author(s)
      Akuta K.、Kashiwagi H.、Yujiri T.、Nishiura N.、Morikawa Y.、Kato H.、Honda S.、Kanakura Y.、Tomiyama Y.
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 17 Issue: 1 Pages: 206-219

    • DOI

      10.1111/jth.14323

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protease-activated receptor-4 (PAR4) variant influences on platelet reactivity induced by PAR4-activating peptide through altered Ca2+ mobilization and ERK phosphorylation in healthy Japanese subjects.2018

    • Author(s)
      Morikawa Y, Kato H, Kashiwagi H, Nishiura N, Akuta K, Honda S, Kanakura Y, Tomiyama Y.
    • Journal Title

      Thromb Res.

      Volume: 162 Pages: 44-52

    • DOI

      10.1016/j.thromres.2017.12.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Kindlin-3欠損血小板の血栓形成が明らかにする血栓形成メカニズム2020

    • Author(s)
      加藤恒、伊藤康彦、柏木浩和、西浦伸子、芥田敬吾、小亀浩一、宮田敏行、保仙直毅、金倉譲、冨山佳昭
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血小板機能異常症解析からのメッセージ:血小板血栓制御機構2020

    • Author(s)
      加藤恒
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The critical role of kindlin-3 in initiation of physiological thrombus formation-analysis of kindlin-3 deficient patient2019

    • Author(s)
      Kato H, Honda S, Kashiwagi H, Nishiura N, Akuta K, Kokame K, Miyata T, Tomiyama Y
    • Organizer
      61th American Society of Hematology Annual Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Platelet function of chronic immune thrombocytopenia2019

    • Author(s)
      Nishiura N, Kashiwagi H, Akuta K, Kato H, Kanakura Y, Tomiyama Y
    • Organizer
      The XXVII congress of the international society of thrombosis and haemostasis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規のインテグリンαIIbβ3非活性化変異β3(R734C)を認めた一家系2019

    • Author(s)
      芥田敬吾、柏木浩和、西浦伸子、加藤恒、金倉譲、冨山佳昭
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Platelet Integrin αIIbβ3 Activation Kinetics in Inherited Platelet Functional Disorders; the Role of ADP Receptor P2Y12, Caldag-GEFI and Kindlin-3 αIIbβ3 Activation By inside-out Signaling2018

    • Author(s)
      Hisashi Kato、Nobuko Nishiura、Keigo Akuta、Hirokazu Kashiwagi、Koichi Kokame、Toshiyuki Miyata、Yuzuru Kanakura、Yoshiaki Tomiyama
    • Organizer
      60th American Society of Hematology annual meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血小板機能異常症におけるフィブリノゲン受容体インテグリンαIIbβ3活性化キネティクスの評価2018

    • Author(s)
      加藤 恒、柏木浩和、森川陽一郎、芥田敬吾、西浦伸子、本田繁則、小亀浩市、宮田敏行、金倉譲、冨山佳昭
    • Organizer
      第40回日本血栓止血学会学術集会
    • Related Report
      2018 Research-status Report
  • [Book] 今日の治療薬2020-特発性血小板減少性紫斑病2020

    • Author(s)
      加藤 恒
    • Total Pages
      3
    • Publisher
      南江堂
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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