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Molecular mechanism in pathogenesis of arsenic intoxication-toward forensic molecular toxicological clarification-

Research Project

Project/Area Number 19390187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionWakayama Medical University

Principal Investigator

KIMURA Akihiko  Wakayama Medical University, 医学部, 准教授 (60136611)

Co-Investigator(Kenkyū-buntansha) KONDO Toshikazu  和歌山県立医科大学, 医学部, 教授 (70251923)
ISHIDA Yuko  和歌山県立医科大学, 医学部, 講師 (10364077)
Research Collaborator MUKAIDA Naofumi  金沢大学, がん研究所, 教授 (30182067)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2009: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2008: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2007: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords砒素中毒 / IL-6 / autophagy / Stat3 / ERK / 性差 / estrogen / 腎障害 / Estrogen / autophagic cell death / STAT3
Research Abstract

We analyzed pathophysiological roles of inflammatory cytokine, IL-6, and female sex hormone, estrogen, in arsenite-induced renal injury by using mouse models. We found a crucial involvement of autophagic cell death of renal tubular epithelial cells in pathogenesis of arsenite-induced renal injury. We clarified that IL-6 played a protective role in pathogenesis of arsenite-induced renal injury by reduction of autophagy through suppression of ERK phosphorylation. We also found a gender difference in susceptibility to renal toxicity of arsenite, which was caused by an interference of IL-6/Stat3 signaling by estrogen.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (15 results)

All 2010 2009 2008 2007

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (10 results)

  • [Journal Article] The absence of interleukin-6 enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant extracellular signal-regulated kinase activation.2010

    • Author(s)
      Kimura A, Ishida Y, Wada T, Hisaoka T, Morikawa Y, Sugaya T, Mukaida N, Kondo T.
    • Journal Title

      Am J Pathol. 176(1)

      Pages: 40-50

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The absence of interleukin-6 enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant extracellular signal-regulated kinase activation2010

    • Author(s)
      Akihiko Kimura
    • Journal Title

      American Journal of Pathology 176

      Pages: 40-50

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced acetamino-phen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist.2009

    • Author(s)
      Ishibe T, Kimura A, Ishida Y, Takayasu T, Hayashi T, Tsuneyama K, Matsushima K, Sakata I, Mukaida N, Kondo T.
    • Journal Title

      Lab Invest. 89(1)

      Pages: 68-79

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] IFN-gamma protects cerulein-induced acute pancreatitis by repressing NF-kappa B activation.2007

    • Author(s)
      Hayashi T, Ishida Y, Kimura A, Iwakura Y, Mukaida N, Kondo T.
    • Journal Title

      J Immunol. 178(11)

      Pages: 7385-94

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential roles of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration.2007

    • Author(s)
      Ishida Y, Kimura A, Kondo T, Hayashi T, Ueno M, Takakura N, Matsushima K, Mukaida N.
    • Journal Title

      Am J Pathol. 170(3)

      Pages: 843-54

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Presentation] L-6-Jak-Stat signaling is crucially involved in sodium arsenite-induced renal injury.2010

    • Author(s)
      Kimura A, Ishida Y, Mukaida N, Kondo T.
    • Organizer
      FEBS-Special Meeting 2010- Jak-Stat Signalling: from Basics to Disease
    • Place of Presentation
      Vienna
    • Related Report
      2009 Final Research Report
  • [Presentation] IL-6-Jak-Stat signaling is crucially involved in sodium arsenite-induced renal injury2010

    • Author(s)
      Akihiko Kimura
    • Organizer
      FEBS-Special Meeting 2010- Jak-Stat Signalling : from Basics to Disease
    • Place of Presentation
      University of Veterinary Medicine Vienna, Austria
    • Related Report
      2009 Annual Research Report
  • [Presentation] 砒素およびcisplatinによる腎障害の病態形成におけるautophagyの相反する役割.2009

    • Author(s)
      木村章彦
    • Organizer
      第4回糖尿病と高血圧を考える会」研究会「話題提供」
    • Place of Presentation
      和歌山
    • Year and Date
      2009-08-22
    • Related Report
      2009 Final Research Report
  • [Presentation] マウス急性砒素腎障害モデルにおける薬剤による腎障害におけるautophagyの役割-2つのモデルにおける対照的な役割-2009

    • Author(s)
      木村章彦, 石田裕子, 向田直史, 近藤稔和.
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] IL-6 plays a protective role in arsenite-induced renal injury.2008

    • Author(s)
      Kimura A, Ishida Y, Kondo T.
    • Organizer
      The 7th International Symposium on Advances in Legal Medicine (ISALM)
    • Place of Presentation
      Osaka
    • Related Report
      2009 Final Research Report
  • [Presentation] The absence IL6/STAT3 signals enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant EPK activation.2008

    • Author(s)
      Kimura A, Ishida Y, Mukaida N, Kondo T.
    • Organizer
      7th joint Conference of the International Cytokine Society and the International Society for Interferon and Cytokine Research
    • Place of Presentation
      Montreal
    • Related Report
      2009 Final Research Report
  • [Presentation] マウス急性砒素腎障害モデルにおけるIL-6の役割解析.2008

    • Author(s)
      木村章彦, 石田裕子, 野坂みずほ, 近藤稔和
    • Organizer
      第92次日本法医学会総会
    • Place of Presentation
      長崎
    • Related Report
      2009 Final Research Report
  • [Presentation] IL-6 plays a protective role in arsenite-induced renal injury.2008

    • Author(s)
      木村章彦
    • Organizer
      The 7th International Symposium on Advances in Legal Medicine(ISALM)
    • Place of Presentation
      大阪
    • Related Report
      2008 Annual Research Report
  • [Presentation] The absence IL6/STAT3 signals enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant EPK activation.2008

    • Author(s)
      木村章彦
    • Organizer
      7th joint Conference of the International Cytokine Society and the International Society for Interferon and Cytokine Research
    • Place of Presentation
      Canada Montreal
    • Related Report
      2008 Annual Research Report
  • [Presentation] IL-6 plays a protective role in arsenite-induced renal injury2007

    • Author(s)
      木村 章彦
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      東京都港区グランドプリンスホテル新高輪
    • Year and Date
      2007-11-22
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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