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An investigation of mechanism of progression of kidney disease using renal tubular cells differentiated from ES/iPS cells

Research Project

Project/Area Number 24591211
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKeio University

Principal Investigator

MONKAWA Toshiaki  慶應義塾大学, 医学部, 教授 (80286484)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腎臓 / 尿細管 / ES細胞 / iPS細胞 / miRNA / 分化誘導 / 再生医学
Outline of Final Research Achievements

We developed a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. KSP-positive cells had the capacity to form tubular structures when grown in a 3D culture in Matrigel. Moreover, KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. Human ES cells were not willing to differentiate into tubular cells compared to mouse ES cells. GSK-3β-inhibitor increased KSP-positive cells.
We examined miRNA expression in experimental models of EMT and renal epithelialization using microarray, and found that miR-34c attenuates EMT induced by TGF-β in a mouse tubular cell line. To confirm the effects of miR-34c in vivo, we administered the precursor of miR-34c to mice with unilateral ureteral obstruction, and miR-34c decreased kidney fibrosis.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (7 results)

All 2014 2013 2012

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (6 results)

  • [Journal Article] miR-34c attenuates epithelial-mesenchymal transition and kidney fibrosis with ureteral obstruction2014

    • Author(s)
      Ryuji Morizane, Shizuka Fujii, Toshiaki Monkawa, Ken Hiratsuka, Shintaro Yamaguchi1, Koichiro Homma, Hiroshi Itoh
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1

    • DOI

      10.1038/srep04578

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] miR-363 Induces Transdifferentiation of Human Tubular Cells to Mesenchymal Phenotype.2014

    • Author(s)
      Ryuji Morizane, Toshiaki Monkawa, Shizuka Fujii, Hiroshi Itoh
    • Organizer
      Kidney Week
    • Place of Presentation
      米国フィラデルフィア
    • Year and Date
      2014-11-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] miR-34c Ameliorates Renal Fibrosis via Down-Regulation of Jagged1.2013

    • Author(s)
      Ryuji Morizane, Toshiaki Monkawa, Shizuka Fujii, Hiroshi Itoh
    • Organizer
      Kidney Week
    • Place of Presentation
      米国アトランタ
    • Related Report
      2013 Research-status Report
  • [Presentation] Differentiation of Human Embryonic Stem Cells into Kidney Specific Protein Positive Cells.2013

    • Author(s)
      2. Shintaro Yamaguchi, Koichiro Homma, Toshiaki Monkawa, Ryuji Morizane, Sayuri Suzuki, Shizuka Fujii, Shu Wakino, Koichi Hayashi, Hiroshi Itoh
    • Organizer
      Kideny Week
    • Place of Presentation
      米国アトランタ
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトES細胞を用いた尿細管上皮細胞の分化誘導の試み.2013

    • Author(s)
      5. 山口 慎太郎, 本間 康一郎, 門川 俊明, 森實 隆司, 鈴木 さゆり, 藤井 静花, 脇野 修, 林 晃一, 伊藤 裕
    • Organizer
      第56回日本腎臓学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] マウスES細胞を用いた尿細管細胞の分化誘導2012

    • Author(s)
      森實 隆司, 門川 俊明, 伊藤 裕
    • Organizer
      日本腎臓学会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Research-status Report
  • [Presentation] KSP-Positive Cells Derived from Mouse Embryonic Stem Cells Serve as Progenitors of Renal Tubule Cells2012

    • Author(s)
      Ryuji Morizane, Toshiaki Monkawa, Shizuka Fujii, Hiroshi Itoh
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      米国San Diego
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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