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Identification of Hic-5 as a novel regulatory factor for integrin aIIbb3 activation and platelet aggregation in mice.

Research Project

Project/Area Number 23791090
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionShowa University

Principal Investigator

KANEYAMA Shuri  昭和大学, 医学部, 講師 (10338535)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords血栓・止血学 / 血小板 / 細胞接着斑分子 / Hic-5 / インテグリン
Research Abstract

Hic-5, a member of the paxillin family, serves as a focal adhesion adaptor protein associated with aIIbb3. Hic-5 function in aIIbb3 activation and subsequent platelet aggregation remains unknown. To address this question, platelets from Hic-5-/- mice were analyzed. Hic-5-/- mice displayed a significant hemostatic defect and resistance to thromboembolism, which were explained in part by weaker thrombin-induced aggregation in Hic-5-/- platelets. Mechanistically, Hic-5-/- platelets showed limited activation of aIIbb3 upon thrombin treatment. Morphological alteration in Hic-5-/- platelets after thrombin stimulation on fibrinogen plates was also limited. As a direct consequence, the quantity of actin co-immunoprecipitating with the activated aIIbb3 was smaller in Hic-5-/- platelets than in wild-type platelets.We identified Hic-5 as a novel and specific regulatory factor for thrombin-induced aIIbb3 activation and subsequent platelet aggregation in mice.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (42 results)

All 2014 2013 2012 2011 Other

All Journal Article (19 results) (of which Peer Reviewed: 17 results) Presentation (20 results) (of which Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Identification of Hic-5 as a Novel Scaffold for the MKK4/p54 JNK Pathway in the Development of Abdominal Aortic Aneurysms2014

    • Author(s)
      Lei XF, Kim-Kaneyama JR, Arita-Okubo S, Offermanns S, Itabe H, Miyazaki T, Miyazaki A
    • Journal Title

      J Am Heart Assoc

      Volume: 3(3)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Hic-5 as a novel scaffold for the MKK4/p54 JNK pathway in the development of abdominal aortic aneurysms2014

    • Author(s)
      Xiao-Feng Lei, Joo-ri Kim-Kaneyama, Shigeko Arita, Stefan Offermanns, Hiroyuki Itabe, Takuro Miyazaki, Akira Miyazaki
    • Journal Title

      JOURNAL OF THE AMERICAN HEART ASSOCIATION

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血小板凝集の直接の担い手であるαIIbβ3の活性化制御を介することが、抗CD41 Calpain and atherosclerosis2013

    • Author(s)
      Miyazaki T, Koya T, Kigawa Y, Oguchi T, Lei XF, Kim-Kaneyama JR, Miyazaki A
    • Journal Title

      J Atheroscler Thromb

      Volume: 20(3) Pages: 228-37

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Calpain and atherosclerosis.2013

    • Author(s)
      Miyazaki T, Koya T, Kigawa Y, Oguchi T, Lei XF, Kim-Kaneyama JR, Miyazaki A.
    • Journal Title

      J Atheroscler Thromb

      Volume: 20(3) Pages: 228-37

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of Hic-5 as a novel regulatory factor for integrinαIIbβ3 activation and platelet aggregation in mice2012

    • Author(s)
      Kim-Kaneyama JR, Miyauchi A, Lei XF, Arita S, Mino T, Takeda N, Kou K, Eto K, Yoshida T, Miyazaki T, Shioda S, Miyazaki A
    • Journal Title

      J Thromb Haemost

      Volume: 10(9) Pages: 1867-74

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen peroxide-inducible clone 5 (Hic-5) as a potential therapeutic target for vascular and other disorders2012

    • Author(s)
      Kim-Kaneyama JR, Lei XF, Arita S, Miyauchi A, Miyazaki T, Miyazaki A
    • Journal Title

      J Atheroscler Thromb

      Volume: 19(7) Pages: 601-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen peroxide-inducible clone 5 (Hic-5) as a potential therapeutic target2012

    • Author(s)
      Kim-Kaneyama JR
    • Journal Title

      Seikagaku

      Volume: 84(4) Pages: 261-5

    • NAID

      10030741340

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Salusin-βaccelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro2012

    • Author(s)
      Koya T, Miyazaki T, Watanabe T, Shichiri M, Atsumi T, Kim-Kaneyama JR, Miyazaki A
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 303(1)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen Peroxide-Inducible Clone 5 (Hic-5) as a Potential Therapeutic Target for Vascular and Other Disorders2012

    • Author(s)
      Kim-Kaneyama JR, Lei XF, Arita S, Miyauchi A, Miyazaki T, Miyazaki A.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 19 Issue: 7 Pages: 601-607

    • DOI

      10.5551/jat.10736

    • NAID

      130004444615

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Salusin-β accelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro.2012

    • Author(s)
      Koya T, Miyazaki T, Watanabe T, Shichiri M, Atsumi T, Kim-Kaneyama JR, Miyazaki A.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 303(1)

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrogen peroxide-inducible clone 5 (Hic-5) as a potential therapeutic target.2012

    • Author(s)
      Kim-Kaneyama JR
    • Journal Title

      Seikagaku

      Volume: 84(4) Pages: 261-5

    • NAID

      10030741340

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of Hic-5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice.2012

    • Author(s)
      Kim-Kaneyama JR, Miyauchi A, Lei XF, Arita S, Mino T, Takeda N, Kou K, Eto K, Yoshida T, Miyazaki T, Shioda S, Miyazaki A
    • Journal Title

      J Thromb Haemost

      Volume: 10(9) Pages: 1867-74

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis2011

    • Author(s)
      Miyazaki T, Taketomi Y, Takimoto M, Lei XF, Arita S, Kim-Kaneyama JR, Arata S, Ohata H, Ota H, Murakami M, Miyazaki A
    • Journal Title

      Circulation

      Volume: 124(23) Pages: 2522-32

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice2011

    • Author(s)
      Nagashima M, Watanabe T, Terasaki M, Tomoyasu M, Nohtomi K, Kim-Kaneyama JR, Miyazaki A, Hirano T
    • Journal Title

      Diabetologia

      Volume: 54(10) Pages: 2649-59

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling2011

    • Author(s)
      Kim-Kaneyama JR, Takeda N, Sasai A, Miyazaki A, Sata M, Hirabayashi T, Shibanuma M, Yamada G, Nose K
    • Journal Title

      J Mol Cell Cardiol

      Volume: 50(1) Pages: 77-86

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] インクレチンの正常ヒト大動脈血管平滑筋細胞に対する増殖抑制効果についての検討2011

    • Author(s)
      友安雅子,金山朱里,長嶋理晴,寺崎道重,宮崎章,平野勉
    • Journal Title

      糖尿病

      Volume: 54(Supplement 1)

    • Related Report
      2013 Final Research Report
  • [Journal Article] インクレチンのヒト大動脈血管平滑筋細胞に対する増殖・遊走抑制効果についての検討2011

    • Author(s)
      友安雅子,金山朱里,長嶋理晴,寺崎道重,宮崎章,平野勉
    • Journal Title

      糖尿病合併症

      Volume: 25(Supplement 1) Pages: 83-83

    • Related Report
      2013 Final Research Report
  • [Journal Article] Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice.2011

    • Author(s)
      Nagashima M, Watanabe T, Terasaki M, Tomoyasu M, Nohtomi K, Kim-Kaneyama J, Miyazaki A, Hirano T.
    • Journal Title

      Diabetologia

      Volume: 54(10) Pages: 2649-59

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis.2011

    • Author(s)
      Miyazaki T, Taketomi Y, Takimoto M, Lei XF, Arita S, Kim-Kaneyama JR, Arata S, Ohata H, Ota H, Murakami M, Miyazaki A.
    • Journal Title

      Circulation

      Volume: 124(23) Pages: 2522-32

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 新規動脈硬化性疾患制御分子Hic-5の機能解析2014

    • Author(s)
      金山朱里
    • Organizer
      第43回日本心脈管作動物質学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Deletion of hydrogen peroxide-inducible clone-5 inhibits atherosclerotic plaque formation in Apolipoprotein E knockout mice2013

    • Author(s)
      ShigekoArita, Joo-ri Kim-Kaneyama, Xiao-Feng Lei, Takuro Miyazaki, Akira Miyazaki
    • Organizer
      第45回日本動脈硬化学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Hic-5 deficiency blocks the development of angiotensin II-induced abdominal aortic aneurysms by inhibiting c-Jun N-terminal kinase 2 in mice2013

    • Author(s)
      金山朱里、雷小峰、有田茂子、宮崎拓郎、宮崎章
    • Organizer
      第21回日本血管生物医学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Calpain-6による動脈硬化病変およびマクロファージpinocytosisの制御2013

    • Author(s)
      宮崎拓郎、礪波一夫、秦勝志、雷小峰、金山朱里、反町洋之、栗原裕基、宮崎章
    • Organizer
      第21回日本血管生物医学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Calpain-6による動脈硬化病変およびマクロファージpinocytosisの制御2013

    • Author(s)
      宮崎拓郎、礪波一夫、秦勝志、雷小峰、金山朱里、反町洋之、栗原裕基、宮崎章
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 新規動脈硬化性疾患制御分子Hic-5の機能解析2013

    • Author(s)
      金山朱里
    • Organizer
      第43回日本心脈管作動物質学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Incretin-based treatments suppress human macrophage foam cell formation and vascular smooth muscle cell migration and proliferation contributing to atherosclerosis prevention2013

    • Author(s)
      M. Tomoyasu, T. Watanabe, J Kaneyama-Kim, M. Terasaki, K. Nohtomi, K. Sato, F. Itoh, A. Miyazaki , and T. Hirano
    • Organizer
      The 49th EASD Annual Meeting
    • Place of Presentation
      Barcelona
    • Related Report
      2013 Final Research Report
  • [Presentation] Deletion of hydrogen peroxide-inducible clone-5 inhibits atherosclerotic plaque formation in Apolipoprotein E knockout mice.2013

    • Author(s)
      13. Shigeko Arita, Joo-ri Kim-Kaneyama, Xiao-Feng Lei, Takuro Miyazaki, Akira Miyazaki.
    • Organizer
      第45回に本動脈硬化総会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Hic-5 deficiency blocks the development of angiotensin II-induced abdominal aortic aneurysms by inhibiting c-Jun N-terminal kinase 2 in mice.2013

    • Author(s)
      金山朱里、雷小峰、有田茂子、宮崎拓郎、宮崎章
    • Organizer
      第21回日本血管生物医学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Hic-5 deficiency blocks the development of angiotensin II-induced abdominal aortic aneurysms in mice2012

    • Author(s)
      Xiao-Feng Lei, Joo-ri Kim-Kaneyama, ShigekoArita, Takuro Miyazaki, Akira Miyazaki
    • Organizer
      第44回日本動脈硬化学会総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] エゼチミブ投与によるブタ心臓周囲脂肪ならびに心筋組織の酸化コレステロール・脂肪酸分画の変動 : GC/MS法による検討2012

    • Author(s)
      島袋充生、大川知奈美、東田真由子、佐藤寛美、黒部裕嗣、高尾正一郎、平田陽一郎、中山泰介、雷小峰、金山朱里、福田大受、山田博胤、佐藤匡央、北川哲也、佐田政隆
    • Organizer
      第60回日本心臓病学会学術集会
    • Place of Presentation
      石川
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of hydrogen peroxide-inducible clone 5 (Hic-5) in atheroscrelotic diseases2012

    • Author(s)
      金山朱里、雷小峰、有田茂子、宮内彩、宮崎章
    • Organizer
      第20回日本血管生物医学会学術集会
    • Place of Presentation
      徳島
    • Related Report
      2013 Final Research Report
  • [Presentation] Hic-5 deficiency blocks the development of abdominal aortic aneurysms in mice2012

    • Author(s)
      Xiao-Feng Lei, Joo-ri Kim-Kaneyama, ShigekoArita, Takuro Miyazaki, Akira Miyazaki
    • Organizer
      The17th international vascular biology meeting
    • Place of Presentation
      Wiesbaden
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of Hic-5 as a novel regulatory factor for integrinαIIbβ3 activation and platelet aggregation in mice2012

    • Author(s)
      Kim-Kaneyama JR, Miyauchi A, Lei XF, Arita S, Mino T, Takeda N, Kou K, EtoK, Miyazaki T, Miyazaki A
    • Organizer
      The17th international vascular biology meeting
    • Place of Presentation
      Wiesbaden
    • Related Report
      2013 Final Research Report
  • [Presentation] Hic-5 deficiency blocks the development of angiotensin II-induced abdominal aortic aneurysms in mice2012

    • Author(s)
      Xiao-Feng Lei, Joo-ri Kim-Kaneyama, Shigeko Arita, Takuro Miyazaki, Akira Miyazaki
    • Organizer
      The 17th International Vascular Biology Meeting
    • Place of Presentation
      Wiesbaden, Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] Hic-5 deficiency inhibits the development of angiotensin II-induced aortic aneurysms2012

    • Author(s)
      Xiao-Feng Lei, Joo-ri Kim-Kaneyama, Shigeko Arita, Takuro Miyazaki, Akira Miyazaki
    • Organizer
      第44回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling2011

    • Author(s)
      金山朱里
    • Organizer
      第43回日本動脈硬化学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Native incretins supress the proliferation and migration of vascular smooth muscle cells2011

    • Author(s)
      Tomoyasu M, Kim-Kaneyama JR et al.
    • Organizer
      第3回アジア糖尿病学会
    • Place of Presentation
      北京
    • Related Report
      2011 Research-status Report
  • [Presentation] Kim-Kaneyama JR, Miyazaki A et al.2011

    • Author(s)
      Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling
    • Organizer
      第43回日本動脈硬化学会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] インクレチンの正常ヒト大動脈血管平滑筋細胞に対する増殖抑制効果についての検討2011

    • Author(s)
      Tomoyasu M, Kim-Kaneyama JR et al.
    • Organizer
      日本糖尿病学会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Book] 血管生物医学事典2011

    • Author(s)
      金山朱里(他150名)
    • Total Pages
      489
    • Publisher
      日本血管生物医学会
    • Related Report
      2011 Research-status Report
  • [Book] 血管生物医学事典 (日本血管生物医学会編集)第一章25, 26 執筆

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www10.showa-u.ac.jp/~biochem/Biochem/Biochem_top.html

    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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