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The impact of HIF-1 activation on respiratory epithelium during hypoxic insults.

Research Project

Project/Area Number 24592322
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionThe Tazuke Kofukai

Principal Investigator

ADACHI Takehiko  公益財団法人田附興風会, 医学研究所 第9研究部, 部長 (90252428)

Co-Investigator(Kenkyū-buntansha) HIROTA Kiichi  関西医科大学, 医学部, 准教授 (00283606)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords低酸素誘導性因子1 / 無気肺 / タイトジャンクション / 肺障害 / HIF-1 / 肺水腫 / 肺胞炎症 / 低酸素
Outline of Final Research Achievements

The respiratory epithelium forms an important barrier against inhaled pollutants and microorganisms, and its barrier function is often compromised during hypoxic insults. Epithelial activation of hypoxia-inducible factor-1 (HIF-1) represents one feature of airway inflammation, but the functional importance of HIF-1 within the respiratory epithelium is largely unknown. We evaluated the impact of HIF-1 activation on loss of epithelial barrier function during hypoxic insults. Involvement of HIF-1 in these protective effects was confirmed using the pharmacological inhibitor YC-1 and the activator of HIF-1 DFX adopting A549 cells derived from alveolar epithelium. Expression of mRNA and protein of an subunit of Namiloride-blockable ENaC, APQ5 and molecules involving in cell-cell tight junction ZO-1, occudin, claudin were investigated. The critical involvement of HIF-1 was demonstrated.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report

Research Products

(17 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Invited: 4 results)

  • [Journal Article] Involvement of hypozia-inducible factors in the dysregulation of oxygen homeostasis in sepsis2015

    • Author(s)
      Hirota K.
    • Journal Title

      Cardiovascular & hematological disorders drug targets.

      Volume: 15 Pages: 29-40

    • DOI

      10.2174/1871529x15666150108115553

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha2015

    • Author(s)
      Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
    • Journal Title

      Nature communication

      Volume: 6 Pages: 1-10

    • DOI

      10.1038/ncomms7153

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 肺胞低酸素と炎症-低酸素誘導性因子活性化の視点から-2014

    • Author(s)
      広田喜一
    • Journal Title

      分子呼吸器病

      Volume: 18 Pages: 73-75

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 肺内酸素環境と肺疾患-低酸素-HIF1-炎症-2014

    • Author(s)
      広田喜一
    • Journal Title

      呼吸器内科

      Volume: 25 Pages: 270-275

    • Related Report
      2014 Annual Research Report
  • [Journal Article] The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner.2014

    • Author(s)
      Kai S, Tanaka T, Matsuyama T, Suzuki K, Hirota K.
    • Journal Title

      Eur J Pharmacol

      Volume: 732C Pages: 43-49

    • DOI

      10.1016/j.ejphar.2014.03.020

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 肺内酸素環境と肺疾患 -低酸素-HIF-炎症-.2014

    • Author(s)
      広田 喜一
    • Journal Title

      呼吸器内科.

      Volume: 25 Pages: 270-275

    • Related Report
      2013 Research-status Report
  • [Journal Article] 肺胞低酸素と炎症 -低酸素誘導性因子活性化の視点から-.2014

    • Author(s)
      広田喜一
    • Journal Title

      分子呼吸器病.

      Volume: 18 Pages: 73-75

    • Related Report
      2013 Research-status Report
  • [Journal Article] 疾患の病態生理学と低酸素誘導性因子.2013

    • Author(s)
      広田喜一
    • Journal Title

      細胞.

      Volume: 45 Pages: 415-418

    • Related Report
      2013 Research-status Report
  • [Journal Article] General Anesthetics Inhibit LPS-Induced IL-1beta Expression in Glial Cells.2013

    • Author(s)
      Tanaka T, Kai S, Matsuyama T, Adachi T, Fukuda K, Hirota K.
    • Journal Title

      Plos one

      Volume: 8 Pages: 82930-82930

    • DOI

      10.1371/journal.pone.0082930

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E1 in vascular-derived cells under non-hypoxic conditions.2013

    • Author(s)
      Suzuki K, Nishi K, Takabuchi S, Kai S, Matsuyama T, Kurosawa S, Adachi T, Maruyama T, Fukuda K, Hirota K.
    • Journal Title

      Peer J

      Volume: 1 Pages: 1-20

    • DOI

      10.7717/peerj.220

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrogen sulfide inhibits hypoxia- but not anoxia-induced hypoxia-inducible factor 1 activation in a von hippel-lindau- and mitochondria-dependent manner.2012

    • Author(s)
      甲斐慎一、田中具治、大条紘樹、原田浩、岸本俊、鈴木堅悟、高淵聡史、竹永敬三、福田和彦、広田喜一
    • Journal Title

      Antioxidants & Redox signaling

      Volume: 16 Pages: 203-216

    • DOI

      10.1089/ars.2011.3882

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia and hypoxia-inducible factor in inflammation2012

    • Author(s)
      Kiichi, Hirota
    • Journal Title

      Chronic Inflammation: Molecular Pathophysiology, Nutritional and Therapeutic Interventions

      Volume: 1 Pages: 51-65

    • Related Report
      2012 Research-status Report
  • [Journal Article] グルタミノリシス2012

    • Author(s)
      広田喜一
    • Journal Title

      実験医学

      Volume: 30 Pages: 2400-2406

    • Related Report
      2012 Research-status Report
  • [Presentation] 炎症・インフラマソームのレドックス制御とTXNIP/HIF-1システム2012

    • Author(s)
      広田喜一
    • Organizer
      第85回日本生化学会 シンポジウム:1S12 低酸素応答が制御する多彩な生命現象 -生理機能の解明から疾患に迫る
    • Place of Presentation
      福岡市博多区国際会議場
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] hypoxia-indicible factorの20年と5つの未解決問題2012

    • Author(s)
      広田喜一
    • Organizer
      第10回がんとハイポキシア研究会
    • Place of Presentation
      横浜市中区横浜開港記念館
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ハイポキシア生物学ー酸素代謝からみる生命現象の方程式2012

    • Author(s)
      広田喜一
    • Organizer
      第47回日本高気圧環境・潜水医学会学術集会
    • Place of Presentation
      札幌市北区北海道大学
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 硫化水素はミトコンドリア依存的に低酸素誘導性遺伝子応答を調節する

    • Author(s)
      広田喜一
    • Organizer
      第16回日本医療ガス学会学術集会
    • Place of Presentation
      東京都千代田区東京ステーションコンファレンス
    • Related Report
      2012 Research-status Report
    • Invited

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

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