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LIF-STAT3 on renal tubular regeneration process examined by Cre/loxP system

Research Project

Project/Area Number 18590902
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

MONKAWA Toshiaki  Keio University, School of Medicine, Instructor (80286484)

Co-Investigator(Kenkyū-buntansha) SHIMODA Kouji  Keio University, School of Medicine, Assistant Professor (00129470)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordskidney / regeneration / Cre-loxP / LIF / Gs15 / Snail1 / Gsl5 / Cre-LoxP / STAT3
Research Abstract

The purpose of this study is to clarify how the genes involved in LIF-gp 130-STAT3 signal systems act on renal tubular regeneration by Cre/loxP transgenic mice. We succeeded in generating LoxP-LIF mice which expressed LIF in cells expressing Cre. Crossing LoxP-LIF mice with alfa-MHC-Cre mice generated mice in which LIF is highly expressed in myocardiocytes. In the mice, distribution pattern of sympathetic neurons and parasympathetic neurons turned into heart failure pattern. On the other hand, we tried to generated mice in which Cre expresses specifically in renal tubular cells in S3 segment of proximal tubules. However, AQP7-Cre and GGT2-Cre mice did not show S3 segments specific expression of Cre.
We analyzed Gsl5-EGFP mice and Gsl5-HB-EGF mice collaborating with Michiko Sekine at Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science. Gsl5 was shown to be localized in the promoter region of core 2 [beta]-1, 6-N-Acetylglucosaminyl transferase, and was shown to be a cis-regulatory element responsible for proximal S3 tubular cell-specific transcription. Utilizing the Gsl5, we generated transgenic mice in which the human heparin-biding EGF-like growth factor (HB-EGF) is specifically expressed in tubular cells in proximal tubule S3 segment. Mice are resistant to diphtheria toxin (DT) because mice HB-EGF does not bind DT. In contrast, human HB-EGF binds DT at high affinity. In Gsl5-HB-EGF, tubular cells in proximal tubule S3 segment were ablated specifically after administration of DT. Using the mice, we clarified the mechanism of acute renal failure and regeneration of tubular cells.
The pathological significance of the tubular epithelial-mesenchymal transition (EMT) in kidney diseases is becoming increasingly recognized. We demonstrated that transcriptional factor Snail is involved in renal tubular EMT and that TGF-beta1 regulates Snail at the transcription and protein degradation levels.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (15 results)

All 2007 2006

All Journal Article (5 results) (of which Peer Reviewed: 2 results) Presentation (10 results)

  • [Journal Article] Snail is involved in the renal epithelial-mesenchymal transition2007

    • Author(s)
      Yoshino J
    • Journal Title

      Biochem Biophys Res Commun 362

      Pages: 63-68

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 腎の再生因子の探索2007

    • Author(s)
      門川 俊明
    • Journal Title

      医学のあゆみ 220

      Pages: 507-510

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] Snail is involved in the renal epithelial-mesenchymal transition2007

    • Author(s)
      Yoshino, J
    • Journal Title

      Biochem Biophys Res Commun 362

      Pages: 63-68

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Search for renal regenerating factors2007

    • Author(s)
      Monakawa, T
    • Journal Title

      gaku-no-Ayumi 220

      Pages: 507-510

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Snail1 is involved in the renal epithelial-mesenchymal transition2007

    • Author(s)
      Yoshino J
    • Journal Title

      Biochem Biophys Res Commun. 362

      Pages: 63-68

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Selective ablation of tubular cells in proximal tubule S3 segment mediated by diphtheria toxin receptor2007

    • Author(s)
      Toshiaki Monkawa
    • Organizer
      米国腎臓学会
    • Place of Presentation
      米国サンフランシスコ
    • Year and Date
      2007-11-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Selective ablation of tubular cells in proximal tubule S3 segment mediated by diphtheria toxin receptor2007

    • Author(s)
      Toshiaki, Monkawa
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2007-11-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ジフテリア毒素受容体を介した近位尿細管S3セグメント特異的除去マウスの作製2007

    • Author(s)
      門川 俊明
    • Organizer
      第50回日本腎臓学会総会
    • 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
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Selective ablation of tubular cells in proximal tubule S3 segment mediated by diphtheria toxin receptor2007

    • Author(s)
      Toshiaki, Monkawa
    • Organizer
      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
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulation of Snail at the Transcription and Protein Degradation in Renal Epithelial-Mesenchymal Transition2006

    • Author(s)
      Jun Yoshino
    • Organizer
      米国腎臓学会
    • Place of Presentation
      米国サンディエゴ
    • Year and Date
      2006-11-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulation of Snail at the Transcription and Protein Degradation in Renal Epithelial-Mesenchymal Transition2006

    • Author(s)
      Jun, Yoshino
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2006-11-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 進行性腎障害におけるサイモシンβ4およびβ10の役割2006

    • Author(s)
      辻 美保子
    • Organizer
      第49回日本腎臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2006-06-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 腎線維化における転写制御因子snailの役割と発現調節機構2006

    • Author(s)
      吉野 純
    • Organizer
      第49回日本腎臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2006-06-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of Thymosin-beta 4 and 10 in renal fibrosis2006

    • Author(s)
      Mihoko, Tsuji
    • Organizer
      apanese Society of Nephrology
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-06-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulation of Snail in renal fibrosis2006

    • Author(s)
      Jun, Yoshino
    • Organizer
      Japanese Society of Nephrology
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-06-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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