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Kidney regeneration by activating stem cell

Research Project

Project/Area Number 18590881
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

HISHKAWA Keiichi  The University of Tokyo, 医学部・附属病院, 客員准教授 (50255460)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsstem cell / regenerative medicine / renal failure / 腎不全
Research Abstract

研究者はこれまでの研究で、腎臓に体性幹細胞が存在し、その機能が転写因子MyoRで制御されることを明らかとした。本研究では腎臓における組織幹細胞がヒトでも存在し、薬物による活性化が可能かを中心に検討した。
まず、泌尿器科との共同研究でヒト腎臓組織にもSP細胞として分離される体性幹細胞が存在することを明らかとした(lnt J Urol. 2008;15:272-274)。さらに、HDAC阻害薬を用いることにより、体性幹細胞活性化を介して慢性腎不全の再生が可能であることを明らかとした(Stem Cells. 2007;25:2469-2475)。具体的には、HDAC阻害薬TSAの投与により、腎臓再生因子であるBMP7の増加が腎臓体性幹細胞であるSP細胞で確認され、進行した腎不全モデルで20%程度の機能回復が得られた。また、HDAC阻害薬が腎臓再生療法に有望である結果が得られたことから、腎臓再生過程でのepigenetics制御およびepigenetics制御薬の応用をin vivo, in vitroで検討した。その結果、腎虚血再還流障害の再生過程におけるエピジェネティックス制御機構が明らかとなり(J Am Soc Nephrol. 2008, in press)、エピジェネティック制御薬によるヒト培養尿細管細胞の線維化抑制作用(J Am Soc Nephrol. 2007;18:58-65)が確認された。今後各種腎不全モデルにおけるエピジェネティック制御薬の効果を検討する予定である。

Report

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

    (14 results)

All 2007 2006 Other

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury.2007

    • Author(s)
      Imai, N. Hishikawa, K, et. al.
    • Journal Title

      Stem Cells 25

      Pages: 2469-75

    • Related Report
      2007 Annual Research Report 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II type 1 receptor blockade prevents decrease in adult stem-like cells in kidney after ureteral obstruction2007

    • Author(s)
      Takeshi Marumo, Keiichi Hishikawa, et. al.
    • Journal Title

      Eur J Pharmacol 573

      Pages: 216-220

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury.2007

    • Author(s)
      Imai, N., Hishikawa, K., Marumo, T., Hirahashi, J., Inowa, T., Matsuzaki, Y., Okano, H., ct al.
    • Journal Title

      Stem Cells 25

      Pages: 2469-2475

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-betal in human renal epithelial cells.2007

    • Author(s)
      Yoshikawa, M., Hishikawa. K., Marumo, T., and Fujita, T.
    • Journal Title

      J Am Soc Nephrol 18

      Pages: 58-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury2007

    • Author(s)
      Imai, N., Hishikawa K., Marumo, T., Hirahashi, J., Inowa, T., Matsuzaki, Y., Okano, H., et. al.
    • Journal Title

      Stem Cells 25

      Pages: 2469-2475

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells2007

    • Author(s)
      Yoshikawa, M., Hishikawa, K., Marumo, T. & Fujita, T.
    • Journal Title

      J Am Soc Nephrol 18

      Pages: 58-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells.2007

    • Author(s)
      Yoshikawa, M., Hishikawa, K., Marumo, T. & Fujita, T.
    • Journal Title

      J Am Soc Nephrol 18

      Pages: 58-65

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Angiotensin II type1 receptor blockade prevents decrease in adult stem-like cells in kidney after ureteral obstruction2007

    • Author(s)
      Takeshi Marumo, Keiichi Hishikawa, et. al.
    • Journal Title

      Eur J Pharmacol 573

      Pages: 216-220

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Stem cells and kidney disease2006

    • Author(s)
      Hishikawa, K., and Fujita, T.
    • Journal Title

      Hypertens Res 29

      Pages: 745-749

    • NAID

      10018561054

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Stem cells and kidney disease2006

    • Author(s)
      Hishikawa, K., and Fujita, T
    • Journal Title

      Hypertens Res 29

      Pages: 745-749

    • NAID

      10018561054

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Aldosterone impairs bone marrow-derived progenitor cell formation2006

    • Author(s)
      Marumo, T., Uchimura, H., Hayashi, M., Hishikawa, K., and Fujita, T
    • Journal Title

      Hypertension 48

      Pages: 490-496

    • Related Report
      2006 Annual Research Report
  • [Presentation] Epigenetics制御による腎臓再生のこころみ2007

    • Author(s)
      菱川慶一
    • Organizer
      第50回日本腎臓学会学術総会
    • Place of Presentation
      浜松
    • Year and Date
      2007-05-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] Epigenetics and Kidney regeneation2007

    • Author(s)
      Keiichi Hishikawa
    • Organizer
      Japanese Society of Nephrology
    • Place of Presentation
      Hamamatsu
    • Year and Date
      2007-05-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://kid-endo.umin.jp/a-3-17.html

    • Related Report
      2006 Final Research Report Summary

URL: 

Published: 2006-04-01   Modified: 2017-05-19  

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