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Analysis of Molecular Mechanisms of Podocyte Injury and Its Prevention

Research Project

Project/Area Number 21591019
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionGunma University

Principal Investigator

HIROMURA Keiju  群馬大学, 大学院・医学系研究科, 准教授 (70292597)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords足細胞 / ネフローゼ症候群 / 蛋白尿 / 細胞内シグナル伝達経路 / DNAメチル化 / 内科 / 腎臓内科 / シグナル伝達 / 糸球体 / 糸球体上皮細胞 / SIRP-α / 糖尿病性腎症 / 糖尿病
Research Abstract

We have examined the molecular mechanisms of podocyte injury and found the 3 following results. 1) Mizoribine directly inhibits puromycin aminonucleoside-induced podocyte injury through the mechanism independent from IMPDH inhibition. 2) The mice that express mutant SIRP. lacking cytoplasmic region show flatted and irregularly arranged foot processes. In addition, the mutant mice are sensitive to diabetic nephropathy, suggesting that SIRP. and its downstream signalling pathway are involved in the progression of diabetic nephropathy. 3) TGF-β1 induces DNA methylation of WT1 promoter in cultured podocytes. However, the degree of DNA methylation was modest, suggesting that the possibility of methylation of the upstream region of that we have examined or methylation of the promoter of WT1-related molecules.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (24 results)

All 2012 2011 2010 2009

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (16 results)

  • [Journal Article] Dendritic Cell-Specific Ablation of the Protein Tyrosine Phosphatase Shpl Promotes Th1 Cell Differentiation and Induces Autoimmunity2012

    • Author(s)
      Kaneko T, Saito Y, Kotani T, Okazawa H, Iwamura H, Sato-Hashimoto M, Kanazawa Y, Takahashi S, Hiromura K, Kusakari S, Kaneko Y, Murata Y, Ohnishi H, Nojima Y, Takagishi K, Matozaki T
    • Journal Title

      J Immunol

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of tacrolimus for induction therapy in ptients with active lupus nephritis2011

    • Author(s)
      Hamatani H, Takeuchi S, Tomioka M, Maeshima A, Kuroiwa T, Nojima Y
    • Journal Title

      Nephrology (Carlton)

      Volume: 16 Pages: 76-86

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The immunosuppressive drug mizoribine directly prevents podocyte injury in puromycin aminonucleoside nephrosis2010

    • Author(s)
      Takeuchi S, Hiromura K, Sakairi T, Takeuchi S, Maeshima A, Kaneko Y, Kuroiwa T, Takeuchi T, Nojima Y
    • Journal Title

      Nephron Exp Nephrol

      Volume: 16(1)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy2010

    • Author(s)
      Tomioka M, Hiromura K, Sakairi T, Takeuchi S, Maeshima A, Kaneko Y, Kuroiwa T, Takeuchi T, Nojima Y
    • Journal Title

      Nephrology (Carlton)

      Volume: 15 Pages: 568-574

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Immunosuppressive Drug Mizoribine Directly Prevents Podocyte Injury in Puromycin Aminonucleoside Nephrosis.2010

    • Author(s)
      Takeuchi S, Hiromura K, et al
    • Journal Title

      Nephron Experimental Nephrology

      Volume: 116

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nestin Is a Novel Marker for Renal Tubulointerstitial Injury in Immunoglobulin A Nephropathy.2010

    • Author(s)
      Tomioka M, Hiromura K, et al
    • Journal Title

      Nephrology

      Volume: 568 Pages: 568-574

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Proteasome Inhibitors on Rat Renal Fibrosis in Vitro and in Vivo.2010

    • Author(s)
      Sakairi T, Hiromura K, et al
    • Journal Title

      Nephrology

      Volume: 16 Pages: 76-86

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Immunosuppressive Drug Mizoribine Directly Prevents Podocyte Injury in Puromycin Aminonucleoside Nephrosis.2010

    • Author(s)
      Takeuchi S, Hiromura K, et al
    • Journal Title

      Nephron Experimental Nephrology (In Press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] SIRPαは糸球体上皮細胞の形態と蛋白尿制御に関与する2012

    • Author(s)
      高橋哲史、廣村桂樹, 他
    • Organizer
      第2回分子腎臓フォーラム
    • Place of Presentation
      京都リサーチパーク(京都)
    • Year and Date
      2012-01-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] A Novel Case of Nephrotic Syndrome Caused by Immune-Mediated Severe2011

    • Author(s)
      Takahashi M, Hiromura K, et al
    • Organizer
      LCAT Deficiency
    • Place of Presentation
      フィラデルフィア
    • Year and Date
      2011-11-12
    • Related Report
      2011 Final Research Report
  • [Presentation] miR-143 contributes to podocyte injury induced by TGF-β12011

    • Author(s)
      Sakairi T, Abe Y Hiromura K, et al
    • Organizer
      第44回アメリカ腎臓学会
    • Place of Presentation
      米国フィラデルフィア
    • Year and Date
      2011-11-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Transforming Growth Factor(TGF)β11 Induced DNA Methylation of Wilms' Tumor Suppressor Gene (WT1) Promoter in Human Podocytes2011

    • Author(s)
      Hamatani H, Hiromura K, et al
    • Organizer
      第44回アメリカ腎臓学会
    • Place of Presentation
      米国フィラデルフィア
    • Year and Date
      2011-11-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Transforming Growth Factor (TGF)-β1 Induced DNA Methylation of Wilms' Tumor Suppressor Gene (WT1) Promoter in Human Podocytes2011

    • Author(s)
      Hamatani H, Hiromura K, et al
    • Organizer
      第43回アメリカ腎臓学会
    • Place of Presentation
      米国フィラデルフィア
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] SIRPαシグナル経路の遮断は糖尿病性腎症を増悪させる2011

    • Author(s)
      高橋哲史、廣村桂樹, 他
    • Organizer
      第55回日本腎臓学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2011-06-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] SIRP-α (Signal-regulatory protein alpha)は糸球体上皮細胞の形態と蛋白尿制御に関与する2011

    • Author(s)
      高橋哲史、廣村桂樹, 他
    • Organizer
      第6回 弥彦ポドサイトセミナー
    • Place of Presentation
      新潟大学駅南キャンパス「ときめいと」(新潟)
    • Year and Date
      2011-03-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] SIRP-αは糸球体上皮細胞の形態と蛋白尿制御に関与する2010

    • Author(s)
      高橋哲史
    • Organizer
      Kidney Frontier 2010
    • Place of Presentation
      第一ホテル東京(東京)
    • Year and Date
      2010-12-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] The Role of SIRPα(SHPS-1)in Experimental Diabetic Nephropathy2010

    • Author(s)
      Takahashi M, Hiromura K, ea al
    • Organizer
      第43回アメリカ腎臓学会
    • Place of Presentation
      米国デンバー
    • Year and Date
      2010-11-19
    • Related Report
      2011 Final Research Report
  • [Presentation] The Role of SIRPα (SHPS-1) in Experimental Diabetic Nephropathy2010

    • Author(s)
      Takahashi M, Hiromura K, et al
    • Organizer
      第43回アメリカ腎臓学会
    • Place of Presentation
      米国デンバー
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] The Role of SIRP α in Podocyte Structure and Function2010

    • Author(s)
      TomiokaM, Hiromura K, et al
    • Organizer
      国際腎臓学会NEXUS京都シンポジウム
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2010-04-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Tubulointerstitial nestin expression as a predictive marker for renal prognosis in IgA nephropathy2010

    • Author(s)
      Tomioka M, Hiromura K, et al
    • Organizer
      国際腎臓学会NEXUS京都シンポジウム
    • Place of Presentation
      日国立京都国際会館(京都)
    • Year and Date
      2010-04-16
    • Related Report
      2011 Final Research Report
  • [Presentation] The Role of SIRPα in Podocyte Structure and Function2010

    • Author(s)
      Tomioka M, Hiromura K, et al
    • Organizer
      国際腎臓学会NEXUS京都シンポジウム
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2010-04-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] SIRPαは系球体上皮細胞の形態と蛋白尿制御に関与する2009

    • Author(s)
      富岡麻衣、廣村桂樹, 他
    • Organizer
      第10回腎不全病態治療研究会
    • Place of Presentation
      全社協灘尾ホール(東京都)
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] SIRPα(SHPS-1)Signaling Pathway Is Involved in Podocyte Structure and Function2009

    • Author(s)
      Tomioka M, Hiromura K, et al
    • Organizer
      第42回アメリカ腎臓学会
    • Place of Presentation
      サンディエゴコンベンションセンター(合衆国、カルフォルニア州)
    • Year and Date
      2009-10-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 糖尿病性腎症におけるSHPS-1シグナル経路に関する検討2009

    • Author(s)
      高橋哲史, 廣村桂樹, 他
    • Organizer
      第52回日本腎臓学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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