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Hypoxia-Inducible Factor as a Therapeutic Target for Acute Respiratory Distress Syndrome

Research Project

Project/Area Number 15K20054
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionYokohama City University

Principal Investigator

TOJO Kentaro  横浜市立大学, 医学部, 助教 (80737552)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsARDS / エネルギー代謝 / 低酸素誘導性因子 / 解糖系 / 急性呼吸促迫症候群 / プロリルヒドロキシラーゼ / 細胞死 / 肺胞上皮細胞 / 代謝リプログラミング / 肺傷害 / プロリルヒドロキシラーゼ阻害
Outline of Final Research Achievements

Bioenegertic failure due to mitochondrial dysfunction underlies the alveolar epithelial injury during acute respiratory distress syndrome (ARDS). In the present study, we demonstrated that inhibition of oxygen sensing prolyl hydroxylases (PHD) protects alveolar epithelial cells from bioenertic failure and cell death caused by experimental ARDS. The protective effects are mediated by HIF-1-dependent enhancement of glycolysis. These findings suggest that acitvation of HIF-1 might be a novel therapeutic approach for ARDS.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2018 2017 2016

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

  • [Journal Article] Enhancement of glycolysis by inhibition of oxygen-sensing prolyl hydroxylases protects alveolar epithelial cells from acute lung injury2018

    • Author(s)
      Tojo Kentaro、Tamada Nao、Nagamine Yusuke、Yazawa Takuya、Ota Shuhei、Goto Takahisa
    • Journal Title

      The FASEB Journal

      Volume: 32 Issue: 4 Pages: 2258-2268

    • DOI

      10.1096/fj.201700888r

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-Induced Apoptosis and Lung Injury in Mice2016

    • Author(s)
      Yusuke Nagamine, Kentaro Tojo, Takuya Yazawa, Shunsuke Takaki, Yasuko Baba, Takahisa Goto, Kiyoyasu Kurahashi
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 55 Issue: 6 Pages: 878-888

    • DOI

      10.1165/rcmb.2015-0266oc

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Metabolic reprogramming by inhibition of prolyl hydroxylases protects alveolar epithelial cells from LPS-neutrophil-induced energy derangements and cell death2017

    • Author(s)
      Kentaro Tojo, Nao Tamada, Yusuke Nagamine, Shuhei Ota, Takahisa Goto
    • Organizer
      Euroanaesthesia 2017, The European Anesthesiology Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prolyl hydroxylase阻害は肺胞上皮細胞の代謝リプログラミングを介してLPS誘導性肺傷害を軽減する2017

    • Author(s)
      東條 健太郎,玉田 尚,長嶺 祐介,矢澤 卓也,太田 周平,後藤 隆久
    • Organizer
      第64回日本麻酔科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-induced Apoptosis and Lung Injury in Mice2016

    • Author(s)
      Yusuke Nagamine, Kentaro Tojo, Takuya Yazawa, Shunsuke Takaki, Yasuko Baba, Takahisa Goto, Kiyoyasu Kurahashi
    • Organizer
      ATS International Conference 2016
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-05-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The hydroxylase inhibitor dimethyloxallyl glycine protects lung epithelial barriers from LPS-induced injury in mice2016

    • Author(s)
      Kentaro Tojo
    • Organizer
      Euroanaesthesia 2016
    • Place of Presentation
      London, UK
    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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