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2002 Fiscal Year Final Research Report Summary

GENE THERAPY OD ACUTE RENAL FAILURE BY CELL CYCLE-REGULATED GENES

Research Project

Project/Area Number 12671029
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TERADA Yoshio  TOKYO MEDICAL AND DENTAL UNIVERSITY, INSTRUCTOR, 大学院・医歯学総合学研究科, 助教授 (30251531)

Project Period (FY) 2000 – 2002
KeywordsWnt-4 / acute renal failure / cell cycle / ischemia / apoptosis / proximal tubule / proliferaion / cyclin
Research Abstract

We investigated the genes which play important roles in the regeneration of renal tubules during renal failure. Wnt-4 is known to be expressed in the mesonephric duct in embryonic development. It is tempting to speculate that the Wnt-4-β-catenin pathway contributes to the recovery from acute renal failure (ARF). In this study we used an in vivo model of ARF rats to clarify the significance of the Wnt-4-β-catenin pathway in ARF. ARF was induced by clamping the rat left renal artery for 1h. At 3, 6, 12, 24, 48, and 72 h after reperfusion, we extracted whole kidney homogenate and total RNA for examination by Western blot analysis and real-time RT-PCR. Wnt-4 mRNAand protein expression were strongly increased at 3-12 h and 6-24 h after ischemia, respectively. In immunohistological examination, Wnt-4 was expressed in the proximal tubules and co- expressed with aquaporin-1, GM130, and PCNA Cyclin Dl and cyclin A were expressed at 24-48 h after reperfusion. In addition, the overexpression of Wnt-4 and β- catenin promoted the cell cycle and increased the promoter activity and protein expression of cyclin Dl in LLC-PK1 cells. Taken together, these data suggest that the Wnt-4-β-catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Wnt-4-β-catenin pathway may regulate the transcription of cyclin Dl and control the regeneration of renal tubules in ARF.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Terada, Y et al.: "Hyperosmolality Activates Akt and regulates apoptosis in renal tubular cells"Kidney International. 60. 553-567 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terada, Y et al.: "Glucocorticoids stimulate p21CIP1 and arrest cell cycle in vitro and in anti-GBM glomerulonephritis"Kidney International. 59. 1706-1716 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okado, T, Terada, Y et al.: "Smad7 mediates transforming growth factor-β-induced apoptosis in mesangial cells"Kidney International. 62. 1178-1186 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terada, Y et al.: "Ligand-regulatable erythropoietin production by plasmid injection and in vivo electroporation"Kidney International. 62. 1966-1976 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [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).

    • Description
      「研究成果報告書概要(和文)」より

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Published: 2004-04-14  

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