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2007 Fiscal Year Final Research Report Summary

Study on cell-specific roles of nudear factor KB in the progression of renal diseases with genetically modified animals

Research Project

Project/Area Number 18590903
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HAYASHI Matsuhiko  Keio University, School of Medicine, Associate Professor (60129608)

Co-Investigator(Kenkyū-buntansha) FUKUDA Seiichi  Keio University, School of Medicine, Instructor (50338026)
Project Period (FY) 2006 – 2007
KeywordsNFκB / nephrotoxic serum nephritis / Cre-recombinase / Lox-P
Research Abstract

At first, to generate mice lines in which Cre-recombinase is expressed only in adipocyte and proximal tubules S3 segment, aquaporin promoter region with Cre-recombinase expression vector was used to. We obtained 7 lines of mouse, although, Cre-recombinase activity was observed in a patchy manner in the proximal tubules S1 and S2 segments. We also examined the expression of Cre-recombinase mRNA expression in various organs and tissues. Strong expression was seen in testis and adipose tissue, while significant expression was also seen in various tissues, such as liver, muscle, and intestine. From these results, we abandoned these lines of mouse for our study.
On the other hand, we have previously developed conditional transgenic mouse, in which IκBΔN, a dominant-negative form of inhibitory factor of NFκB, is expressed in the presence of Cre-recombinase. We obtained double transgenic mouse of IκBΔN conditional transgenic mouse and podocyte-specific Cre-recombinase expressing mouse. Nephrotoxic serum nephritis was induced in this double transgenic mouse and wild-type mouse. Urinary excretion of protein was significantly lower in double transgenic mouse and crescent formation and glomerular changes were less prominent in double transgenic mouse, too. Double transgenic mouse of IκBΔN conditional transgenic mouse and endothelial-cell-specific Cre-recombinase expressing mouse was not born suggesting that endothelial NFκB activity is required to survive during development.
Furthermore, we examined roles of clusterin in renal tubular cell apoptosis and it was suggested that clusterin might facilitate apoptosis.
From these results, it is suggested that NFκB activity in podocytes plays important roles in the pathogenesis of nephrotoxic serum nephritis.

  • Research Products

    (8 results)

All 2008 2007 2006

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] Inhibition of NF-kappaB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis2008

    • Author(s)
      Takase O, Minto AW, Puri TS, Cunningham PN, Jacob A, Hayashi M, Quigg RJ.
    • Journal Title

      Kidney International 73

      Pages: 567-577

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays2008

    • Author(s)
      Takase O, Marumo T, Hishikawa K, Fujita T, Quigg RJ, Hayashi M.
    • Journal Title

      Clinical and Experimental Nephrology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Inhibition of NF-kappaB-dependent Bc1-xL expression by clusterin promotes albumin-induced tubular cell apoptosis2008

    • Author(s)
      Takase, O, Minto, AW, Puri, TS, Cunningham, PN, Jacob, A, Hayashi, M, Quigg, RJ
    • Journal Title

      Kidney International 73

      Pages: 567-577

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] NF-κ B-dependent genes induced by proteinuria and identified using DNA microarrays2008

    • Author(s)
      Takase, O, Marumo, T, Hishikawa, K, Fujita, T, Quigg, RJ, Hayashi, M
    • Journal Title

      Clinical and Experimental Nephrology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] LPS誘発尿細管障害におけるイコサペントエン酸(EPA)のNF-kappaBを中心とした腎保護作用の解明2007

    • Author(s)
      高瀬 敦、菱川 慶一、丸茂 丈史、吉川 真弘、林 松彦、Quigg Richard、藤田 敏郎
    • Organizer
      第50回日本腎臓学会学術総会
    • Place of Presentation
      浜松
    • Year and Date
      2007-05-25
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Study on renal protective effects focused on NF-kappaB of eicosapentoeic acid in LPS-induced renal tubular damage2007

    • Author(s)
      Takase, O, Hishikawa, K, Marumo, F, Yoshikawa, M, Hayashi, M, Richard, Q, Fujita, T
    • Organizer
      The 50th Annual Meeting of Japanese Society of Nephrology
    • Place of Presentation
      Hamamatsu
    • Year and Date
      2007-05-25
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] アルドステロン持続注入ラットにおけるスピロノラクトンとトリアムテレンの腎障害に対する効果の比較2006

    • Author(s)
      福田 誠一、門川 俊明、浅井 昌樹、林松 彦
    • Organizer
      第49回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2006-06-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The effects of spironolactone and triamterene in aldosterone-infused rats2006

    • Author(s)
      Fukuda, S, Monkawa, T, Asai, M, Hayashi, M
    • Organizer
      The 49th Annual Meeting of Japanese Society of Nephrology
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-06-02
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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