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An investigation on the role of HIF-1 in the regulation of microglia activity

Research Project

Project/Area Number 24592336
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKansai Medical University (2013-2014)
Kyoto University (2012)

Principal Investigator

TAKABUCHI Satoshi  関西医科大学, 医学部, 研究員 (90402841)

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マイクログリア / 低酸素誘導性因子1 / 神経因性疼痛 / 酸素代謝 / 自然免疫 / 慢性疼痛 / 脊髄 / 微小環境 / HIF-1
Outline of Final Research Achievements

Microglia is a component equivalent to macrophage serving a critical innate immunity in the central nervous system (CNS). We demonstrate that in response to activation of the microglia cell line BV-2 cells, expression of both HIF-1a and HIF-1b; increases leading to enhanced expression of HIF-1 target genes. Moreover, we also demonstrated that spinal nerve ligation (SNL) in rats dysregulated the spinal oxygen homeostasis and that spinal hypoxia induced HIF-1 activation resulting in increase of mRNA expression of ATP receptors such P2X4 and P2Y7. Our results strongly suggest that increased activation of HIF-1 occurs in the CNS in response to spinal root ligation and that HIF-1 may play a critical role in the establishment of allodynia induced by SNL in which microglia activation is essential.

Report

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

Research Products

(15 results)

All 2015 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Invited: 2 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-HIF-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] 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] 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] 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] Involvement of decreased hypoxia-inducible factor 1 activity and resultant G(1)-S cell cycle transition in radioresistance of perinecrotic tumor cells2013

    • Author(s)
      Y. Zhu, T. Zhao, S. Itasaka, L. Zeng, C.J. Yeom, K. Hirota, K. Suzuki, A. Morinibu, K. Shinomiya, G. Ou, M. Yoshimura, M. Hiraoka, H. Harada
    • Journal Title

      Oncogene

      Volume: 32 Pages: 2058-2068

    • DOI

      10.1038/onc.2012.223

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of n-propyl gallate on neuronal survival after forebrain ischemia in rats2012

    • Author(s)
      Y. Kawano, M. Kawaguchi, K. Hirota, S. Kai, N. Konishi, H. Furuya
    • Journal Title

      Resuscitation

      Volume: 83 Pages: 249-252

    • DOI

      10.1016/j.resuscitation.2011.07.024

    • 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: 51-56

    • 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] マイクログリアの活性化と酸素環境が低酸素誘導性遺伝子発現と神経因性疼痛関連遺伝子発現に与える影響2012

    • Author(s)
      松山 智紀 他
    • Organizer
      日本麻酔科学会 第59回学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2012 Research-status Report
  • [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
    • 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
    • Related Report
      2012 Research-status Report
    • Invited

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

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