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A role of the novel platelet activation receptor CLEC-2 and its internal ligand podoplanin in thrombotic diseases

Research Project

Project/Area Number 20390268
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionUniversity of Yamanashi

Principal Investigator

OZAKI Yukio  University of Yamanashi, 大学院・医学工学総合研究部, 教授 (30134539)

Co-Investigator(Kenkyū-buntansha) INOUE Katsue  山梨大学, 大学院・医学工学総合研究部, 准教授 (10324211)
INOUE Osamu  山梨大学, 大学院・医学工学総合研究部, 助教 (00432154)
SATOH Kaneo  山梨大学, 医学部, 助手 (20242662)
Co-Investigator(Renkei-kenkyūsha) ASADA Yujiro  宮崎大学, 医学部, 教授 (70202588)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2008: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords血小板 / CLEC-2 / ポドプラニン / 血栓症 / podoplanin / 動脈硬化 / 動脈血栓症
Research Abstract

Novel platelet activation receptor CLEC-2 binds to podoplanin expressed on the surface of several kinds of cancer cells, which facilitates cancer metastasis. However, its role in thrombosis and hemostasis has not been elucidated to date. We generated CLEC-2-deficient mice and found that thrombus formation was inhibited in vivo and in vitro. We also found that CLEC-2 forms homophilic association in a manner depending on platelet activation, which stabilizes thrombus formation. Tail bleeding was not significantly increased in CLEC-2-deficient platelets, suggesting that CLEC-2 may be a good target protein for anti-platelet drug, which inhibits pathological thrombosis, but not physiological hemostasis.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (28 results)

All 2011 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 5 results) Presentation (12 results) Book (4 results) Remarks (3 results)

  • [Journal Article] The novel platelet activation receptor CLEC-2.2011

    • Author(s)
      井上克枝, 井上修, 尾崎由基男
    • Journal Title

      Platelet In press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The novel platelet activation receptor CLEC-22011

    • Author(s)
      Katsue Suzuki-lnoue, et al.
    • Journal Title

      Platelet

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新規血小板受容体CLEC-2の同定と機能2010

    • Author(s)
      井上克枝、井上修、尾崎由基男
    • Journal Title

      臨床病理 58

      Pages: 1193-1202

    • NAID

      10029426637

    • Related Report
      2010 Final Research Report
  • [Journal Article] Essential in vivo roles of the C-type lectin receptor CLEC-2: embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconnections and impaired thrombus formation ofCLEC-2-deficient platelets.2010

    • Author(s)
      井上克枝, 井上修, (10名), 尾崎由基男
    • Journal Title

      J Biol Chem 285

      Pages: 24494-24507

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential in vivo roles of the C-type lectin receptor CLEC-2 : embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconne coons and impaired thrombus formation of CLEC-2-deficient platelets2010

    • Author(s)
      Katsue Suzuki-Inoue, et al.
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 24494-507

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新規血小板受容体CLEC-2の同定と機能2010

    • Author(s)
      井上克枝, 他
    • Journal Title

      臨床病理

      Volume: 58 Pages: 1193-1202

    • NAID

      10029426637

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 新規血小板活性化受容体CLEC-22009

    • Author(s)
      井上克枝
    • Journal Title

      日本血栓止血学会誌 20(4)

      Pages: 401-405

    • NAID

      10026117808

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] Novel interactions in platelet biology : CLEC-2/podoplanin and laminin/GPVI.2009

    • Author(s)
      尾崎由基男, 井上克枝, 井上修
    • Journal Title

      J Thromb. Haemost. Suppl. 1

      Pages: 191-194

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel interactions in platelet biology : CLEC-2/podoplanin and laminin/GPVI.2009

    • Author(s)
      Ozaki Y
    • Journal Title

      J Thromb.Haemost. Suppl.1

      Pages: 191-4

    • Related Report
      2009 Annual Research Report
  • [Presentation] Essential in vivo roles of the C-type lectin receptor CLEC-2 : embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconnections and impaired thrombus formation of CLEC-2-deficient platelets.2011

    • Author(s)
      井上克枝
    • Organizer
      血液血管オルビス
    • Place of Presentation
      東京
    • Year and Date
      2011-08-21
    • Related Report
      2010 Final Research Report
  • [Presentation] The novel platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation and migration of lymphatic endothelial cells.2010

    • Author(s)
      井上克枝
    • Organizer
      The American Society of Hematology Annual Meeeting
    • Place of Presentation
      Orland
    • Year and Date
      2010-12-04
    • Related Report
      2010 Final Research Report
  • [Presentation] The novel platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation and migration of lymphatic endothelial cells.2010

    • Author(s)
      Makoto Osada, et al.(Presented by Katsue Suzuki-Inoue)
    • Organizer
      The American Society of Hematology Annual Meeeting
    • Place of Presentation
      USA(Orland)
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規血小板活性化受容体CLEC-2の同定と機能2010

    • Author(s)
      井上克枝
    • Organizer
      臨床検査医学会(学会賞受賞講演(学術賞))
    • Place of Presentation
      東京
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Essential in vivo roles of the C-type lectin receptor CLEC-2 : embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconne ctions and impaired thrombus formation of CLEC-2-deficient platelets.2010

    • Author(s)
      Katsue Suzuki-Inoue, et al.
    • Organizer
      血液血管オルビス
    • Place of Presentation
      東京
    • Year and Date
      2010-08-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規血小板活性化受容体CLEC-2のリンパ管発生における役割2010

    • Author(s)
      井上克枝
    • Organizer
      日本血栓止血学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 新規血小板活性化受容体CLEC-2の血栓止血における役割2010

    • Author(s)
      井上修
    • Organizer
      日本血栓止血学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 新規血小板活性化受容体CLEC-2.シンポジウム2S7a「血栓症の分子メカニズム:最近の進歩」2009

    • Author(s)
      井上克枝
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 新規血小板活性化受容体CLEC-2.シンポジウム2S7a「血栓症の分子メカニズム:最近の進歩2009

    • Author(s)
      井上克枝
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] A role of platelet membrane microdomains in CLEC-2-mediated signal transduction.2009

    • Author(s)
      井上克枝
    • Organizer
      XXII The international Society on Thrombosis and Haemostasis
    • Place of Presentation
      Boston
    • Year and Date
      2009-07-16
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Novel interactions in platelet biology. State of the Art lectures.2009

    • Author(s)
      Ozaki Y.
    • Organizer
      XXII The international Society on Thrombosis and Haemostasis
    • Place of Presentation
      Boston
    • Year and Date
      2009-07-14
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] CLEC-2信号伝達系における血小板膜マイクロドメインの役割2009

    • Author(s)
      井上克枝
    • Organizer
      第32回日本血栓止血学会学術集会
    • Place of Presentation
      小倉
    • Year and Date
      2009-06-09
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Book] 個体発生における血小板の役割(井上分)(Annual Review 血液)(坂田洋一他編集)2011

    • Author(s)
      井上克枝
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] 「個体発生における血小板の役割」坂田洋一他編集Annual Review血液20112011

    • Author(s)
      井上克枝
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report
  • [Book] がんと血小板(井上分)(Annual Review 血液)(坂田洋一他編集)2010

    • Author(s)
      井上克枝
    • Total Pages
      8
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] 「がんと血小板」Annual Review血液2010(坂田洋一他編集)2010

    • Author(s)
      井上克枝
    • Total Pages
      8
    • Publisher
      中外医学社(井上分)
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www.med.yamanashi.ac.jp/clinical/clin0lab/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/clin01ab/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/clin0lab/

    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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