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2004 Fiscal Year Final Research Report Summary

Gene analysis and molecular drug discovery of ADPKD

Research Project

Project/Area Number 15591713
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionTeikyo University

Principal Investigator

HORIE Shigeo  Teikyo Univ, Dept. of Urology. School of Medicine, Professor and Chairman, 医学部, 教授 (40190243)

Project Period (FY) 2003 – 2004
KeywordsADPKD / polycystin-1 / endothelin-1 / MAPK / PWV / vascular endothelial function
Research Abstract

In the Pkd1^<-/-> kidney, the renal parenchyma of Pkd1^<-/-> had numerous cysts. The hearts of Pkd1^<-/-> had a double-outlet right ventricle (DORV) and ventricular septal defect (VSD). It is well known that DORV is observed in endothelin-l(ET-1) deficient mice. ET-1 regulate ERK activation. So, to investigate whether polycystin-1 would regulate the ET-1 pathway, mouse embryonic fibroblast (MEF) was stimulated with ET-1 and the phosphorylation of ERK was examined with gel shift assay. The phosphorylation was hardly admitted in Pkd1^<-/-> MEF compared with Pkd1^<+/+> and Pkd1^<+/-> MEF. Moreover, the high osmotic pressure stimulation is known to the stimulation that activates ERK excluding ET-1. When the activation of ERK in the high osmotic pressure stimulation was examined to examine whether it was the one ET-1 peculiar a previous result, the phosphorylation was hardly admitted in Pkd1^<-/-> MEF compared with Pkd1^<+/+> and Pkd1^<+/-> MEF. MAPK activates AP-1, and adjusts the gene expression such as c-MYC. Pkd1^<-/-> has been intentionally decreasing the appearance of c-MYC by heart compared with a wild type. These results suggested that polycystin-1 take part in Pkd1^<-/-> in the signal transmission of MAPK/ERK2.
Ankle Brachial Index (ABI) and Pulse Wave Velocity (PWV) were measured for 18 ADPKD patients. These data showed good reverse-correlation between PWV, ABI and Ccr (PWV : P=0.0006, ABI : P=0.0285). Moreover, renal volume intentionally correlated only to PWV (P=0.0364).
These data suggests that the relation to the progress of renal failure and vascular endothelial function, and the possibility of a molecular drug development was expected.

  • Research Products

    (8 results)

All 2005 2004

All Journal Article (8 results)

  • [Journal Article] Pkd1 regulates immortalized proliferation of renal tubular epithetlial cells through p53 induction and JNK activation.2005

    • Author(s)
      Nishio S, Hatano M, Nagata M, Horie S, Koike T, Tokuhisa T, Mochizuki T
    • Journal Title

      J Clin Invest.

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease.2005

    • Author(s)
      Nutahata K, Higashihara E, Horie S, et al.
    • Journal Title

      Nephron Clin Pract 99(1)

      Pages: C18-C23

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation.2005

    • Author(s)
      Nishio S, Hatano M, Nagata M, Horie S, Koike T, Tokuhisa T, Mochizuki T.
    • Journal Title

      J Clin Invest.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease.2005

    • Author(s)
      Nutahara K, Higashihara E, Horie S, et al.
    • Journal Title

      Nephron Clin Pract. 99(1)

      Pages: C18-23

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Evidence for the presence of angiogenin in human testis2004

    • Author(s)
      Koga K, Osuga Y, Yano T, Ikezuki Y, Yoshino O, Hirota Y, Hirata T, Horie S, Ayabe T, Tsutsumi O, Taketani Y
    • Journal Title

      J Androl. 25(3)

      Pages: 369-374

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Detection of circulating MUC7-positive cells by reverse transcription-polymerase chain reaction in bladder cancer patients2004

    • Author(s)
      Kinuo M, Okegawa T, Horie S, Nutahara K, Higashihara E.
    • Journal Title

      Int J Urol 11(1)

      Pages: 38-43

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Evidence for the presence of angiogenin in human testis.2004

    • Author(s)
      Koga K, Osuga Y, Yano T, Ikezuki Y, Yoshino O, Hirota Y, Hirata T, Horie S, Ayabe T, Tsutsumi O, Taketani Y.
    • Journal Title

      J Androl. 25(3)

      Pages: 369-74

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Detection of circulating MUC7-positive cells by reverse transcription- Polymerase chain reaction in bladder cancer patients.2004

    • Author(s)
      Kinjo M, Okegawa T, Horie S, Nutahara K, Higashihara E.
    • Journal Title

      Int J Urol. 11(1)

      Pages: 38-43

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

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Published: 2006-07-11  

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