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Exploring the crosstalk between resident fibroblasts and tubular epithelial cells in the kidney

Research Project

Project/Area Number 25860677
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionKyoto University

Principal Investigator

IGUCHI TAKU  京都大学, 医学(系)研究科(研究院), 研究員 (30644504)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords慢性腎臓病 / 細胞間クロストーク / AKI to CKD / 尿細管障害と線維化 / 近位尿細管-線維芽細胞間クロストークの存在
Outline of Final Research Achievements

To analyze the function of fibroblasts and proximal tubular epithelial cells in the kidney, we utilized Cre recombination and diphtheria toxin receptor (DTR) system. DT administration for the mice expressing DTR in fibroblasts triggered the expression of tubular injury markers, as well as the proliferation of proximal tubule cells. To search for the molecules supporting tubular cells, we performed microarray analysis and identified several signaling pathways down-regulated by DT administration.
Meanwhile, DT administration for the mice DTR expressing in proximal tubular cells caused severe proximal tubule-specific injury associated with interstitial fibrosis. Mild proximal tubule injury from a single injection of low-dose DT triggered reversible fibrosis, whereas repeated mild injuries caused sustained interstitial fibrosis.
These results support the existence of crosstalk between fibroblasts and tubular cells, and the signaling pathways may be the target for new therapeutics.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (7 results)

All 2016 2015 2014

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Severity and Frequency of Proximal Tubule Injury Determines Renal Prognosis2016

    • Author(s)
      Takaori K, Nakamura J, Yamamoto S, Nakata H, Sato Y, Takase M, Nameta M, Yamamoto T, Economides AN, Kohno K, Haga H, Sharma K, Yanagita M.
    • Journal Title

      Journal of American Society of Nephrology

      Volume: 未 Issue: 8 Pages: 2393-2406

    • DOI

      10.1681/asn.2015060647

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Severity, Frequency and Prevalence of Proximal Tubule Injury Determines2015

    • Author(s)
      Koji Takaori
    • Organizer
      American Society of Nephrology kidney week 2015
    • Place of Presentation
      San Diego
    • Year and Date
      2015-11-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] AKI to CKD Continuumにおける障害近位尿細管の役割2015

    • Author(s)
      高折光司
    • Organizer
      第58回 日本腎臓学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] レチノイドシグナルを介した尿細管上皮-線維芽細胞相互作用の解明2015

    • Author(s)
      中村仁
    • Organizer
      第58回 日本腎臓学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] Exploring the Pathophysiological Functions of Resident Fibroblasts in the Kidney2014

    • Author(s)
      中村 仁
    • Organizer
      アメリカ腎臓学会
    • Place of Presentation
      フィラデルフィア
    • Year and Date
      2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 近位尿細管障害は線維化,遠位尿細管障害およびアルブミン尿を惹起する2014

    • Author(s)
      高折 光司
    • Organizer
      日本腎臓学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-06
    • Related Report
      2014 Research-status Report
  • [Presentation] 慢性腎臓病における上皮 - 線維芽細胞相互作用の解明2014

    • Author(s)
      中村 仁
    • Organizer
      日本腎臓学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-05
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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