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

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11470337
• Research Category: Grant-in-Aid for Scientific Research (B).
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Osaka 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
• Keywords: Chronic Rejection / Renal Transplantation / Glucocorticoid Receptor / Gel Shift / Immunosuppression / Stero'd

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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