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Elucidation of the role of kindlin in the functional expression of beta3 integrins and investigation of the kindlin-related new molecules

Research Project

Project/Area Number 15K09463
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Honda Shigenori  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (00303959)

Co-Investigator(Kenkyū-buntansha) 宮田 敏行  国立研究開発法人国立循環器病研究センター, 病院, 非常勤研究員 (90183970)
Co-Investigator(Renkei-kenkyūsha) Tomiyama Yoshiaki  大阪大学, 医学研究科, 准教授 (80252667)
Research Collaborator Ikejima Hiroko  国立循環器病研究センター, 研究所, 研究補助者
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインテグリン / シグナル伝達
Outline of Final Research Achievements

β3 integrins are heterodimeric adhesion receptors and members of the integrin superfamily consisted of αIIbβ3 and αVβ3. αIIbβ3, a major integrin expressed on platelets, is critical for platelet aggregation mediated by bindings of fibrinogen and von Willebrand factor. αVβ3 (also called vitronectin receptor), an integrin widely expressed on several cell types including blood vessel tissue constitutive cells and tumor cells, is involved in diverse vascular disease states, tumor proliferation and metastasis.
Kindlins function as an integrin activator that interacts with intracellular proteins such as integrin-linked kinase (ILK). We have reported that ILK is associated with integrin activation. In this study, we investigated the role of each domain of Kindlin-3 in αIIbβ3 activation, and it was suggested that each subdomain could have an important role in αIIbβ3 activation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2018 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [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
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human CalDAG-GEFI deficiency increases bleeding and delays αIIbβ3 activation.2016

    • Author(s)
      Kato H, Nakazawa Y, Kurokawa Y, Kashiwagi H, Morikawa Y, Morita D, Banno F, Honda S, Kanakura Y, Tomiyama Y.
    • Journal Title

      Blood

      Volume: 128 Issue: 23 Pages: 2729-2733

    • DOI

      10.1182/blood-2016-03-704825

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency.2016

    • Author(s)
      Fan X, Kremer Hovinga JA, Shirotani-Ikejima H, Eura Y, Hirai H, Honda S, Kokame K, Taleghani MM, von Krogh AS, Yoshida Y, Fujimura Y, Lammle B, Miyata T
    • Journal Title

      Int J Hematol

      Volume: 103 Issue: 3 Pages: 283-291

    • DOI

      10.1007/s12185-015-1933-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] The association of PAR4 polymorphism with human platelet reactivity in Japanese.2016

    • Author(s)
      Morikawa Y, Kato H, Akuta K, Kashiwagi H, Honda S, Kanakura Y, Tomiyama Y
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] トロンビン受容体PAR4多型性の血小板機能における意義2016

    • Author(s)
      森川洋一郎, 加藤 恒, 芥田敬吾, 柏木浩和, 本田繁則, 金倉 譲, 冨山佳昭
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良市
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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