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Effective treatment of HGF for chronic rejection after living renal transplantation

Research Project

Project/Area Number 10307036
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

OKUYAMA Akihiko  Graduate School of Medicine, Osaka University Professor, 医学系研究科, 教授 (20093388)

Co-Investigator(Kenkyū-buntansha) KANEDA Yasushi  Graduate School of Medicine, Osaka University Professor, 医学系研究科, 教授 (10177537)
TAKAHARA Shiro  Graduate School of Medicine, Osaka University Associate Professor, 医学系研究科, 助教授 (70179547)
KITAHURA Masaya  Graduate School of Medicine, Osaka University Associate Professor, 医学系研究科, 助手 (70273688)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥20,300,000 (Direct Cost: ¥20,300,000)
Fiscal Year 1999: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1998: ¥12,100,000 (Direct Cost: ¥12,100,000)
KeywordsHGF / Reual transplantation / rejection / gene therapy
Research Abstract

(1) Effect of HGF on nephrotoxicity of tacrolimus
A model for drug-induced nephropathy was made by giving tacrolimus to SHR rat. Recombinant HGF was given continuously by osmotic pump and 10days after, serum creatinine significantly increased only in control group. In HGF group, histopathological examination showed little specific findings for drug induced nephropathy such as vacuolization of distal tubules, showing protective effect of HGF against renal damage.
(2) Effect of HGF on chronic rejection after renal transplantation
A model for chronic rejection was made by transplanting a kidney from F344 rat to nephrectomized Lew rat orthotopically. By injecting recombinant HGF intravenously for 28 days, all rats in HGF group survived up to 32 weeks after transplantation, while in control group, 12 rats out of 24 died. In control group, many indicators for inflammation or fibrosis, such as ICAM-1, α-SMA, MCP-1, IL-6, TGF, TNF-α increased, while in HGF group no significant change of such indicators was observed.
(3) Preliminary experiment for gene therapy of HGF against nephropathy
Gene induction of HGF by HVJ-liposome method was studied either by intra muscular injection, intra ureteral injection or injection into renal artery. By intra muscular injection, we got the most stable expression of 0.1ng/ml HGF in the serum. By using ischemic model, we found decreased apoptosis in HGF group by Tunnel method but we could not conclude protective effect of gene induction of HGF because there were no difference of serum creatinine between two groups. In 5/6 nephrectomized model, 3/4 in HGF group and 3/5 in control group died after 15-25 weeks and no conclusion was made by that experiment. However, the examination of the kidney of survived rats revealed the inhibition of mesangial proliferation in HGF group.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 高原史郎ほか: "薬剤性腎毒性(ラットモデル)に対するhHGFおよびFTSの効果と機序"Organ Biology. 5. 98 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shingo Takada et al.: "Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity In spontanously hypertensive rats"Transplant Iut. 12. 27-32 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruto Azuma et al.: "Effect of hepatocyte growth factor on chronic rejection in rat renal allografts"Transplant Proc.. 31. 854-855 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shingo Takada et. al.: "Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats."Transplant Int.. 12. 27-32 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruto Azuma et. al.: "Effect of hepatocyte growth factor on chronic rejection in rat reval allograffs"Transplant Proc.. 31. 854-855 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahara. S.: "The Effects and Mechanisms of HGF and FTS on Pivg Induced Renal Damage in Rat"Organ Biology. 5. 98 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 高原史郎 ほか: "薬剤性腎毒性(ラット・モデル)に対するhHGFおよびFTSの効果と機序"Organ Biology. 5. 98 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Singo Takada et al.: "Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats"Transplant Int.. 12. 27-32 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haruto Azuma et al.: "Effect of hepatocyte growth factor on chronic rejection in rat renal allografts"Treusplant Proc.. 31. 855-855 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高原史郎,市丸直嗣,北村雅哉ら: "薬剤性腎毒性(ラット・モデル)に対するhHGFおよびFTSの効果と機1序" Organ Biology. 5・2. 98 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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