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Analysis of regulatory mechanism of sustained integrin alphaIIbbeta3 activation.

Research Project

Project/Area Number 26461403
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

Kato Hisashi  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, 准教授 (80252667)
Co-Investigator(Renkei-kenkyūsha) Tomiyama Yoshiaki  大阪大学, 医学部附属病院・輸血部, 准教授 (80252667)
Research Collaborator Ichii Michiko  大阪大学, 大学院医学系研究科・血液・腫瘍内科, 寄付講座助教 (30633010)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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)
KeywordsインテグリンαIIbβ3 / Inside-Outシグナル / CalDAG-GEFI / 血小板 / インテグリン活性化 / 血栓 / inside-outシグナル
Outline of Final Research Achievements

Platelet fibrinogen receptor integrin αIIbβ3 is essential for hemostasis and its activation state is tightly regulated by inside-out signaling. So far, the detailed mechanism how inside-out signaling induces activation of αIIbβ3 is still obscure. In this study, we determined the molecules which are important for inside-out signaling in the megakaryocytic cell line CMK and the patient with CalDAG-GEFI deficiency who has been suffering severe bleeding problems. However, platelets with CalDAG-GEFI deficiency showed mildly impaired αIIbβ3 activation. And we found the delayed αIIbβ3 activation in CalDAG-GEFI deficient platelets is related to severe bleeding symptoms. Our results indicate the importance of CalDAG-GEFI and αIIbβ3 activation kinetics for normal hemostasis (Blood 2016).

Report

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

    (14 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [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 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Interaction of kindlin-2 with integrin beta3 promotes outside-in signaling responsed by the alphavbeta3 vitronectin receptor.2015

    • Author(s)
      Liao Z, Kato H, Pandey M, Cantor JM, Ablooglu AJ, Ginsberg MH, Shattil SJ
    • Journal Title

      Blood

      Volume: 125 Issue: 12 Pages: 1995-2004

    • DOI

      10.1182/blood-2014-09-603035

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical significance of IPF% or RP% measurement in distinguishing primary immune thrombocytopenia from aplastic thrombocytopenic disorders.2015

    • Author(s)
      Sakuragi M, Hayashi S, Maruyama M, Kabutomori O, Kiyokawa T, Nagamine K, Kato H, Kashiwagi H, Kanakura Y, Tomiyama Y.
    • Journal Title

      Int J Hematol.

      Volume: 101 Issue: 4 Pages: 369-375

    • DOI

      10.1007/s12185-015-1741-0

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] インテグリンαIIbβ3の構造変化と活性化:talinによる活性化機構2014

    • Author(s)
      加藤恒、冨山佳昭
    • Journal Title

      日本血栓止血学会誌

      Volume: 25 Pages: 619-628

    • NAID

      130004700441

    • Related Report
      2014 Research-status Report
  • [Presentation] 血小板機能異常症の診断 ―まれな出血傾向を見逃さないために―2016

    • Author(s)
      加藤 恒
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Integrin inside-out activation: the role of CalDAG-GEFI in platelet integrinαIIbβ3 activation2016

    • Author(s)
      加藤 恒
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良春日野国際フォーラム(奈良県奈良市)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Severe bleeding tendency and impaired platelet fuction in a patient with CalDAG-GEFI deficiency2015

    • Author(s)
      加藤 恒、中沢洋三、盛田大介、黒川由美、柏木浩和、森川陽一郎、金倉 譲、冨山佳昭
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ホテル金沢(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Severe bleeding tendency and impaired platelet fuction in a patient with CalDAG-GEFI deficiency2015

    • Author(s)
      Hisashi Kato, Yozo Nakazawa, Hirokazu Kashiwagi, Seiji Tadokoro, Yoichiro Morikawa, Morita Daisuke, Kurokawa Yumi, Yuzuru Kanakura, Yoshiaki Tomiyama
    • Organizer
      The 25th Congress of the International Society on Thrombosis and Haemostasis.
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinical significance of IPF% or RP% measurement in distinguishing primary immune thrombocytopenia from aplastic thrombocytopenic disorders.2015

    • Author(s)
      SakuragiM, Hayashi S, Maruyama M, Kabutomori O, Kiyokawa T, Nagamine K, Kato H, Kashiwagi H, Kanakura Y, Tomiyama Y.
    • Organizer
      The 25th Congress of the International Society on Thrombosis and Haemostasis.
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ITP診断における網状血小板測定の臨床的意義~FCM法、IPF法(XN-1000とXE-2100)の比較検討~2015

    • Author(s)
      林悟、櫻木美基子、丸山美保、兜森修、清川知子、永峰敬丞、加藤恒、柏木浩和、金倉譲、冨山佳昭
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府総合市民会館(山梨県甲府市)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report
  • [Presentation] αIIbβ3活性化変異、αIIb(R995W)KIマウスは巨大血小板減少症とともに血小板機能障害をきたす2015

    • Author(s)
      柏木浩和、清水一旦、國島伸司、坂野史明、加藤恒、森川陽一郎、田所誠司、小亀浩市、本田繁則、宮田敏行、金倉譲、冨山佳昭
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府総合市民会館(山梨県甲府市)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
  • [Presentation] alphaIIb(R990W), a constitutive activation mutation of integrin alphaIIbbeta3, kock-in mice show macrothrombocytopenia with impairment of platelet function.2014

    • Author(s)
      Kiyomizu K, Kashiwagi H, Kunishima S, Banno F, Kato H, Morikawa Y, Tadokoro S, Kokame K, Honds S, Miyata T, Kanakura Y, Tomiyama Y
    • Organizer
      The American Society of Hematology 56th annual meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-08
    • Related Report
      2014 Research-status Report
  • [Presentation] αIIbβ3活性化変異、αIIb(R990W)ノックインマウスは巨大血小板減少症を伴う血小板無力症様の表現型を示す2014

    • Author(s)
      清水一亘、柏木浩和、国島信治、坂野史明、森川陽一郎、加藤恒、田所誠司、小亀浩市、本田繁則、宮田敏行、金倉譲、冨山佳昭
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] インテグリンαIIbβ3活性化変異、αIIb(R990W)ノックインマウスの解析2014

    • Author(s)
      清水一亘、柏木浩和、国島信治、坂野史明、森川陽一郎、加藤恒、田所誠司、小亀浩市、本田繁則、宮田敏行、金倉譲、冨山佳昭
    • Organizer
      第36回日本血栓止血学会学術集会
    • Place of Presentation
      大阪国際交流センター、大阪
    • Year and Date
      2014-05-30
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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