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腎糸球体および尿細管細胞の再生医学の腎疾患治療への検討への応用

Research Project

Project/Area Number 14657251
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

佐々木 成  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (60170677)

Co-Investigator(Kenkyū-buntansha) 寺田 典生  東京医科歯科大学, 大学院・医歯学総合研究科, 助教授 (30251531)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsEts-1 / Wnt-4 / 急性腎不全 / HGF / Activin / cyclin D / cyclin A / 細胞周期 / ES細胞 / 腎尿細管細胞 / 糸球体上皮細胞 / Wnt4 / aquaporin2 / nephrin / E2F1 / 幹細胞 / 尿細管細胞 / 上皮細胞 / Nephrin
Research Abstract

本研究において、尿細管再生に関わる研究としては、マウスES細胞および内因性幹細胞様尿細管細胞を用いて尿細管幹細胞の分化再生をおこなった。申請者は、マウスES細胞をEB(embryoid body)細胞に分化させる際、HGFおよび、Activinを添加すると水チャネル(Aquaporin 2)を発現することを確認している。このことは、ES細胞から集合尿細管細胞を分化、誘導できることが、示唆され、さらに尿細管を再生できる可能性がある。また申請者は、胎生期にのみ腎に発現し、尿細管細胞の発生、分化に関与するWnt4と、尿細管細胞の細胞増殖に関与する転写因子E2F1に注目した。急性腎不全(ARF)での近位尿細管細胞は一旦細胞がapoptosisあるいは、necrosisに陥り脱落するが、24-48時間の間に、近位尿細管細胞は再生し、盛んに分裂、増殖をし、近位尿細管は再生する。このときの再生、増殖の時期に、Wnt4とE2F1が近位尿細管が劇的に発現亢進することを、ラットの虚血性急性腎不全モデルにおいて申請者らは、はじめて確認し、アメリカ腎臓病学会にて発表した。Ets-1の発現により、cyclin D1,cyclin Aの転写亢進がおこり、尿細管細胞の再生、分化が誘導されると考えられる。これらの知見は腎細胞の再生の研究の一助になるものと考えられる。

Report

(3 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (12 results)

All 2004 Other

All Journal Article (1 results) Book (1 results) Publications (10 results)

  • [Journal Article] Expression and function of Ets-1 during experimental acute renal failure in rats2004

    • Author(s)
      Tanaka H, Terada Y et al.
    • Journal Title

      Journal of American Society of Nephrology 15

      Pages: 3083-3092

    • Related Report
      2004 Annual Research Report
  • [Book] 尿量の異常.講議録、腎臓学2004

    • Author(s)
      岡戸友和, 寺田典生
    • Publisher
      Medical View社
    • Related Report
      2004 Annual Research Report
  • [Publications] Terada Y et al.: "Wnt4 Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats"J Am Soc Nephrol. 14. 1223 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimamura H et al.: "The PI3-kinase-Akt pathway promotes mesangial cell survival and inhibited apoptosis in vitro via NF-kB and Bad"J Am Soc Nephrol. 14. 1427 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Asai T et al.: "Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations"Kidney International. 64. 2 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashita Y et al.: "Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure"Infectious Diseases Review. 1. 8 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terada Y et al.: "Ligand-regulatable erythropoietin production by plasmid injection and in vivo electroporation"Kidney International. 62. 1966-1976 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Terada Y et al.: "Gene transfer and expression of SMAD7 using adenovirus combined with in vivo electroporation in unilateral ureteral obstruction in rats"Kidney International. 61. S94-S98 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Terada Y et al.: "Wnt4 Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats"Journal of American Society of Nephrology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Okado T, Terada Y et al.: "Smad7 mediates transforming growth factor-β-induced apoptosis in mesangial cells"Kidney International. 62. 1178-1186 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoshita S, Takeda T.Takai Y, Terada Y et al.: "Phosphorylation and inactivation of Mcl-1 by c-Jun N-terminal kinase (JNK) in response to oxidative stress"Journal of Biological Chemistry. 277. 43730-43735 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuwahara M, Ohta T, Gu Y, Asai T, Terada Y, et al.: "Renal expression of metallothionein in rats treated with cadmium"Clinical & Expimental Nephrology. 6. 79-84 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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