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)
|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)
(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.