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Activated hepatic stellate cell specific antibody that attenuates liver fibrosis: mechanism of action and therapeutic use

Research Project

Project/Area Number 24659367
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

YOKOSAKI Yasuyuki  広島大学, 保健管理センター, 准教授 (80210607)

Co-Investigator(Kenkyū-buntansha) KANNO Keishi  広島大学, 病院, 助教 (30448237)
Co-Investigator(Renkei-kenkyūsha) SENTANI Kazuhiro  広島大学, 医歯薬保健学研究院, 助教 (30508164)
NISHIMICHI Norihisa  広島大学, 保健管理センター, 研究員 (00583486)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsインテグリン / 線維症 / 星細胞 / TGF-β / 抗体医薬 / 肝硬変 / 肝線維化 / 肺線維化 / 阻害抗体 / 筋線維芽細胞 / モノクロナル抗体
Research Abstract

We have previously generated an anti-integrin alpha8beta1 blocking antibody, which has been found to inhibit liver fibrosis in mouse models. In the present study, we aimed at the mechanism of the profibrotic activity of integrin alpha8beta1. We found that 1) alpha8beta1 activates TGF-beta that plays major roles in fibrosis, and 2) alpha8beta1 supports emergence of myofibroblast that is a constituent of fibrotic tissues. The activation was previously fond also in other integrins, but the myofibroblast induction was a novel finding.

Report

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

    (22 results)

All 2014 2013 2012 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (16 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Deletion of tetraspanin CD9 diminishes lymphangiogenesis in vivo and in vitro.2013

    • Author(s)
      Iwasaki T, Takeda Y, Maruyama K, etc
    • Journal Title

      J Biol Chem.

      Volume: 288 Issue: 4 Pages: 2118-2131

    • DOI

      10.1074/jbc.m112.424291

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Myofibroblast Differentiation Mediated By Integrin α8β1.2014

    • Author(s)
      Norihisa Nishimichi, Keishi Kanno, Akiko Sugiyama, Yasuyuki Yokosaki
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone, CO, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新しい肺線維化抑制薬シーズインテグリンα8β1阻害抗体2014

    • Author(s)
      横崎恭之、西道教尚、仙谷和弘、菅野啓司、安井弥
    • Organizer
      第54日本呼吸器学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] Inhibition Of Pulmonary Fibrosis By Integrin α8β1 Blocking Antibody and TGFβ-Independent Myofibroblast Differentiation By α8β1 Mediated Signal2014

    • Author(s)
      Y. Yokosaki, N. Nishimichi, K. Kanno, K. Sentani
    • Organizer
      American Thoracic Society 2014 International Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] α8β1 Integrin And Mechanical Traction Are Necessary For Activation Of TGFβ In Fibroblasts2014

    • Author(s)
      N.M. Mark, C. Hung, Y-H. Chow, K. Kennewick, S. Lewis, N. Nishimichi, Y. Yokosaki, B. Hinz, L.M. Schnapp
    • Organizer
      American Thoracic Society 2014 International Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] A possible therapeutic agent for pulmonary fibrosis : antibody against integrinα8β12013

    • Author(s)
      Yokosaki Y, Nishimichi N, Kanno K, Senatani K, Yasui W.
    • Organizer
      European Respiratory Society
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] Role ofα8β1 integrin in TGF-βactivation by lung fibroblasts2013

    • Author(s)
      Nick Mark, Chi Hung C, Yu-Hua Chow, Norihisa Nishimichi, Lynn Schnapp, Yasuyuki Yokosaki
    • Organizer
      American Thoracic Society 2013 International Meeting
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of α8β1 integrin in TGF-β activation by lung fibroblasts2013

    • Author(s)
      Nick Mark, Chi Hung C, Yu-Hua Chow, Norihisa Nishimichi, Lynn Schnapp, Yasuyuki Yokosaki.
    • Organizer
      American Thoracic Society 2013 International Meeting
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] A possible therapeutic agent for pulmonary fibrosis: antibody against integrin α8β1.2013

    • Author(s)
      Yokosaki Y, Nishimichi N, Kanno K, Senatani K, Yasui W.
    • Organizer
      European Respiratory Society
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] インテグリンα8β1機能阻害モノクローナル抗体の認識部位の同定2012

    • Author(s)
      西道教尚、横崎恭之
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] インテグリンα8β1は活性化肝星細胞に発現し肝線維化を促進する2012

    • Author(s)
      西道教尚、菅野啓司、仙谷和弘、安井弥、横崎恭之
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Integrinα8β1 as a new therapeutic target for tissue fibrosis. American Thoracic Society2012

    • Author(s)
      Norihisa Nishimichi, Keishi Kanno, Neil C. Henderson, Dean Sheppard, Yasuyuki Yokosaki
    • Organizer
      2012 International Meeting
    • Place of Presentation
      San Francisco, CA, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] インテグリンとVEGFR-3の仲介役テトラスパニンCD9はリンパ節転移(リンパ管新生)を促進する2012

    • Author(s)
      岩崎剛雄,武田吉人,横崎恭之,辻野和之,木島貴志,立花功,川瀬一郎,熊ノ郷淳
    • Organizer
      第52回日本呼吸器学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] インテグリンとVEGFR-3の仲介役テトラスパニンCD9はリンパ節転移 (リンパ管新生) を促進する2012

    • Author(s)
      岩崎剛雄, 武田吉人, 横崎恭之, 辻野和之, 木島貴志, 立花功, 川瀬一郎, 熊ノ郷淳
    • Organizer
      第52回日本呼吸器学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Integrin α8β1 As A New Therapeutic Target For Tissue Fibrosis2012

    • Author(s)
      Norihisa Nishimichi, Keishi Kanno, Neil C. Henderson, Dean Sheppard, Yasuyuki Yokosaki
    • Organizer
      American Thoracic Society, 2012 International Meeting
    • Place of Presentation
      San Francisco, CA, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] インテグリンα8β1 機能阻害モノクローナル抗体の認識部位の同定2012

    • Author(s)
      西道教尚、横崎恭之
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] インテグリンα8β1 は活性化肝星細胞に発現し肝線維化を促進する2012

    • Author(s)
      西道教尚、菅野啓司、仙谷和弘、安井弥、横崎恭之
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://home.hiroshima-u.ac.jp/integrin/Home.html

    • Related Report
      2013 Final Research Report
  • [Remarks] インテグリン治療開発フロンティア研究室

    • URL

      http://home.hiroshima-u.ac.jp/integrin/Home.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] インテグリン治療開発フロンティア研究室

    • URL

      http://home.hiroshima-u.ac.jp/integrin/Home.html

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] インテグリンα8β1の機能を阻害する事による線維化の抑制2013

    • Inventor(s)
      横崎恭之、西道教尚
    • Industrial Property Rights Holder
      広島大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-03-28
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] インテグリンα8β1の機能を阻害する事による線維化の抑制2013

    • Inventor(s)
      横崎恭之
    • Industrial Property Rights Holder
      広島大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-03-28
    • Related Report
      2012 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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