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Differences in binding of glucocorticoid receptor to DNA in Chronic renal graft rejection.

Research Project

Project/Area Number 11470337
Research Category

Grant-in-Aid for Scientific Research (B).

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

Principal Investigator

KOKADO Yukito  Osaka University Graduate School of Medicine, Lecturer., 医学系研究科, 講師 (30186639)

Co-Investigator(Kenkyū-buntansha) NONOMURA Norio  Osaka University Graduate School of Medicine, Professor Lecturer, 医学系研究科, 講師 (30263263)
TAKAHARA Shiro  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70179547)
OKUYAMA Akihiko  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (20093388)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsChronic Rejection / Renal Transplantation / Glucocorticoid Receptor / Gel Shift / Immunosuppression / Stero'd / 転写因子 / 免疫抑制
Research Abstract

Although chronic rejection is the most common reason for late allograft loss, its pathophysiology and etiology are unclear. Attempts to prevent chronic rejection are now focused on the modulation of transcriptional regulation. We evaluated the ability of glucocorticoid receptors (GR) to bind to the DNA binding site in peripheral blood mononuclear cells (PBMC) of five patients with chronic rejection and seven without it. Using an electrophoretic mobility shift assay, we measured the amount of nuclear glucocorticoid receptor capable of binding to its specific DNA recognition sequences, termed glucocorticoid response elements (GRE). GR binding was significantly greater in control patients than in those with chronic rejection (P<0.01). The retarded band was almost undetectable in two patients with chronic rejection even though they were taking more prednisolone than the seven control patients, all of whom had clearly identifiable retarded bands. These results suggest a decreased ability of GR to bind to GRE in chronic rejection, resulting in a reduced ability to block key proinflammatory promoter sites. This reduced binding may be one molecular basis of chronic rejection.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] N.Ichimaru,Y.Kokado: "Differences in binding of glucocorticoid receptor to DNA in chronic renal rejection"Transplant Int. 13. 255-259 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nishimura,S.Takahara: "Prostate stromal cell-derived HGF induces invasion of DO145"Prostate. 41. 145-143 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Azuma,S.Takahara: "HGF prevents development of chronic allograft nephropathy in rats"J Am Soc Nephrol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nishimura, M.Kitamura, H.Miura, N.Nonomura, S.Takada, , S.Takahara, K.Matsumoto, T.Nakamura and A.Okuyama: "Prostate stromal cell-derived hepatocyte growth factor induced invasion of prostate cancer cell line DU145 through tumor-stromal interaction."Prostate. 41. 145-153 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Ichimaru, S.Takahara (corresponding author), J.D.Wang, K.Toki, Y.Kokado andf A.Okuyama: "Differences in binding of glucocorticoid receptor (GR) to DNA in chronic renal graft rejection."Transplant Int. 13. 255-259 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Azuma, S.Takahara, K.Matsumoto, N.Ichimaru, J.D.Wang, T.Moriyama, A Wega, M.Kitamura, Y.Otsuki, A.Okuyama, Y.Katsuoka, A.Chandraker, M.Sayegh and T.Nakamura: "Hepatocyte growth factor prevents development of chronic allograft nephropathy in rats."J Am Soc Nephrol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Ichimaru,Y.Kodado, et al.: "Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine and tackolimus"Atherosclerosis. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Hosotsubo,Y.Kokado, et al: "Rapid and simultaneous determination of mycophenolic acid and its glucuronic conjugate in human plasma by HPLC using isocratic elution"J Chromatography. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Oka,Y.Kokado, et al: "A clinical study of IgA nephropathy in renal transplant recipients"Nephrol Dial Transplant. 15. 689-695 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Toki,Y.Kokado, et al.: "Arteriolopathy in non-episode biopsies of renal transplant allografts"Clin Transplantation. 14(suppl). 33-36 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Kokado,S.takahara, et al.: "Factors influencing vertebral bone density after renal transplantation"Transplant Int. 13(suppl). 431-435 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Toki,Y.Kokado, et al: "Clinicopathological evaluation in non-episode biopsies of renal transplant allograft"Transplant Int.. 13(suppl). 73-77 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Toki,Y.Kokado,et al.: "Arteriolopathy in non-episode biopsies of renal transplant"Clin Transplantation. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Toki,Y.Kokado,et al.: "Clinicopathological evaluation in non-episode biopsies"Transplant Int. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] J,D,Wang,Y.Kokado,et al.: "Early induction of apoptosis in androgen-independent prostate cancer cell line by FTY720"The Prostate. 40. 50-55 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Takahashi,Y.Kokado,et al.: "Acute renal allograft rejection in the canine : Evaluation with serial duplex doppler ultrasonography"Transplant Proc. 31. 1731-1734 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Kokado,S.Takahashi,et al.: "Low-dose tacrolimus (FK506)-based immunosuppressive protocol in living donor renal transplantation"Transplant Proc. 31. 1151-1154 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Takahashi,Y.Kokado,et al.: "Effect of Hepatocyte growth factor on tacrolimus-induced nephyotoyicity in rats"Transplant Int. 12. 27-32 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小角幸人,高原史朗: "腎移植とタクロリムス"六法出版社. 6 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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