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2007 Fiscal Year Final Research Report Summary

Analysis of anti-platelet and anti-thrombotic effects of a neuron guidance molecule,semaphorin 3A

Research Project

Project/Area Number 18599004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

KASHIWAGI Hirokazu  Osaka University, Graduate School of Medicine, Assistant Professor (10432535)

Co-Investigator(Kenkyū-buntansha) TOMIYAMA Yoshiaki  Osaka University, Hospital, Associate Professor (80252667)
Project Period (FY) 2006 – 2007
KeywordsPlatelet / Thrombosis / semaphoring 3A / signal transduction / PI3 kinase
Research Abstract

(1) Effects of Sena3A on thrombosis and atherosclerosis
To express large amount of Sema3A in vivo, we made Sema3A-adenovirus. We used an in vivo thrombosis model by irradiation of helium-neon laser to Evans blue injected mice. By monitoring the production of thrombosis under video-microscope, we analyzed effects of Sema3A on thrombosis production.
(2) Analysis of anti-platelet mechanism of Sema3A
To elucidate the inhibitory mechanism of platelet function by Sema3A, we investigated the impacts of Sema3A on platelet activating signaling induced by thrombin or convubxin. Sema3A did not affect thrombin-induced PKC activation. In contrast, Sema3A markedly inhibited P2Y_12 and PI3 kinase-dependent AKT activation induced by thrombin. Addition of excessive ADP could not restore the inhibition of AKT activation by Sema3A. Sema3A also inhibited thrombin-induced Rap1 activation, which appeared to be regulated by PI3 kinase activity. Sema3A inhibited not only thrombin but also convulxin-induced AKT and Rapl activation, whereas it did not affect convulxin-induced phosphorylation of LAT, SLP-76, PLC□2, or PKC substrates. These results suggested that irrespective of the type of agonists, Sema3A antagonizes PI3 kinase pathway induced by agonists in platelets.

  • Research Products

    (28 results)

All 2007 2006

All Journal Article (16 results) (of which Peer Reviewed: 6 results) Presentation (12 results)

  • [Journal Article] Adiponectin binds to chemokines via the globular head andmodulates interactions between chemokines and heparan sulfates2007

    • Author(s)
      Masaie H, et. al.
    • Journal Title

      Experimental Hematology 35

      Pages: 947-956

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Semaphorin3Aによる血小板機能抑制2007

    • Author(s)
      柏木 浩和、冨山 佳昭
    • Journal Title

      Angiology Frontier 6

      Pages: 216-222

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 血栓形成のメカニズムup-to-date2007

    • Author(s)
      冨山 佳昭
    • Journal Title

      Angiology Frontier 6

      Pages: 11-17

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Adiponectin binds to chemokines via the globular head andmodulates interactions between chemokines and heparan sulfates2007

    • Author(s)
      Masaie, H, et. al.
    • Journal Title

      Experimental Hematology 35

      Pages: 947-956

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of platelet function by Semaphorin 3A2007

    • Author(s)
      Kashiwagi, H, Tomiyama, Y
    • Journal Title

      Angiology Frontier[Japanese] 6

      Pages: 216-222

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mechanism of thrombus formation : up-to-date2007

    • Author(s)
      Tomiyama, Y
    • Journal Title

      Angiology Frontier[Japanese] 6

      Pages: 11-17

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Critical role of ADP interaction with P2Y receptor in the maintenance of αIIbβ3 activation: association with Rap1B activation2006

    • Author(s)
      Kamae T, et. al.
    • Journal Title

      Journal of Thrombosis and Haemostasis 4

      Pages: 1379-1387

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura2006

    • Author(s)
      Banno F, et. al.
    • Journal Title

      Blood 107

      Pages: 3161-3166

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Identification of amino-terminal region of adiponectin as a physiologically functional domain.2006

    • Author(s)
      Ujiie H, et. al.
    • Journal Title

      Journal of Cell Biochemistry 98

      Pages: 194-207

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of CD27 on peripheral CD4^+ T-lymphocytes correlates with the development of severe acute graft-versus-host disease after allogeneic bone marrow transplantation.2006

    • Author(s)
      Yoshida H, et. al.
    • Journal Title

      International Journal of Hematology 84

      Pages: 367-376

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 血小板寒冷凝集素により偽性血小板減少症を呈した4例2006

    • Author(s)
      倉田義之、et. al.
    • Journal Title

      臨床血液 47

      Pages: 781-786

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Critical role of ADP interaction with P2Y receptor in the maintenance of αIIbβ3 activation : association with Rap1B activation2006

    • Author(s)
      Kamae, T, et. al.
    • Journal Title

      Journal of Thrombosis and Haemostasis 4

      Pages: 1379-1387

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura2006

    • Author(s)
      Banno, F, et. al.
    • Journal Title

      Blood 107

      Pages: 3161-3166

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of amino-terminal region of adiponectin as a physiologically functional domain2006

    • Author(s)
      Ujiie, H, et. al.
    • Journal Title

      Journal of Cell Biochemistry 98

      Pages: 194-207

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of CD27 on peripheral CD4' T-lymphocytes correlates with the development of severe acute graft-versus-host disease after allogeneic bone marrow transplantation2006

    • Author(s)
      Yoshida, H, et. al.
    • Journal Title

      International Journal of Hematology 84

      Pages: 367-376

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Four cases of pseudothrombocytopenia due to platelet cold agglutinins2006

    • Author(s)
      Kurata, Y, et. al.
    • Journal Title

      Rinsho Ketsueki [Japanese] 47

      Pages: 781-786

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 抗GPVI抗体に起因すると思われるGPVI欠損症の一例2007

    • Author(s)
      秋山正夫, et. al.
    • Organizer
      第30回日本血栓止血学会学術集会
    • Place of Presentation
      三重
    • Year and Date
      20071115-17
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] A case of GPVI deficiency caused by and-GPVI autoantibodies2007

    • Author(s)
      Akiyama, M, et. al.
    • Organizer
      The 30th annual Meeting of Japanese Society of Thrombosis and Hemostasis
    • Place of Presentation
      Mie, Japan
    • Year and Date
      20071115-17
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Semaphorin 3A antagonizes agonist-induced PI3 kinase pathway in platelets2007

    • Author(s)
      Akiyama M, et. al.
    • Organizer
      XXI Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Geneva, Switzerland
    • Year and Date
      20070706-12
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Semaphorin 3A inhibits platelet function via PI3 kinase-dependent pathways2007

    • Author(s)
      Akiyama M, et. al.
    • Organizer
      The 5th Aso International Meeting
    • Place of Presentation
      Aso, Japan
    • Year and Date
      20070517-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] P2Y_<12>-independent transient activation and P2Y_<12>-dependnet prolonged activation of platelet integrin α_<IIb>β_32006

    • Author(s)
      Shiraga M, et. al.
    • Organizer
      The American Society of Hematology 48th Annual meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      20061209-12
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Shiraga, M., et. al. P2Y_12-independent transient activation and P2Y_12-dependnet prolonged activation of platelet integrin a_11bB_32006

    • Author(s)
      Shiraga, M, et. al.
    • Organizer
      The American Society of Hematology 48th Annual meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      20061209-12
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Semaphorin 3AはPI3 kinase系を介して血小板機能を抑制する2006

    • Author(s)
      秋山正夫, et. al.
    • Organizer
      第29回日本血栓止血学会学術集会
    • Place of Presentation
      栃木
    • Year and Date
      20061116-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Semaphorin 3A antagonize agonist-induced PI3 kinase pathway in platelets2006

    • Author(s)
      Akiyama, M, et. al.
    • Organizer
      The 29th Annual Meeting of Japanese Society of Thrombosis and Hemostasis
    • Place of Presentation
      Tochigi, Japan
    • Year and Date
      20061116-18
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Semaphorin 3AはPI3 kinase系を介して血小板機能を抑制する2006

    • Author(s)
      秋山正夫, et. al.
    • Organizer
      第68回日本血液学会総会・第48回日本臨床血液学会総会 合同開催
    • Place of Presentation
      福岡
    • Year and Date
      20061006-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Semaphorin 3A inhibits platelet function via PI3 kinase-dependent pathways2006

    • Author(s)
      Akiyama, M, et. al.
    • Organizer
      The 68th Annual Meeting of Japanese Society of Hematology/ The 48th Annual Meeting of Japanese Society of Clinical Hematology
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      20061006-08
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Positive and negative regulation of GPIIb/IIIa function2006

    • Author(s)
      Tomiyama Y
    • Organizer
      The 4th Asian-Pacific Congress on Thrombosis and Hemostasis
    • Place of Presentation
      Suzhou, China
    • Year and Date
      20060921-22
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Positive and negative regulation of GPIIbQHa function2006

    • Author(s)
      Tomiyama, Y
    • Organizer
      The 4th Asian-Pacific Congress on Thrombosis and Hemostasis
    • Place of Presentation
      Suzhou, China
    • Year and Date
      20060921-22
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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