Gene therapy of ischemic-damaged kidney in the rat using hepatocyte growth factor gene

Abstract

IMMUNOSUPPRESSIVE reagents are generally the only therapy available to prevent rejection after renal transplantation. No effective drug for chronic rejection has been established. Hepatocyte growth factor (HGF) is a multifunctional cytokine that induces the regeneration of damaged kidneys, and we first used it for the treatment of tacrolimus-induced nephrotoxicity. Recently, we reported the successful use of HGF for the treatment of chronic rejection after renal transplantation. In that study, recombinant HGF was injected intravenously daily for 4 weeks (100 mg/d) into rats with a renal allograft; all of the treated animals survived, whereas 54.2% of the rats in the control group died within 32 weeks. This experiment proved that cytokine can reduce chronic rejection, suggesting ischemic damage is at least the main part of the phenomena. The problem for the clinical use of this therapy is that a tremendous amount of HGF and frequent injections are required because HGF is metabolized very quickly by the liver. To overcome such limitations, gene therapy with the HGF gene was used successfully in the treatment of liver cirrhosis using a hemagglutinating virus of Japan (HVJ) liposome. This study was designed to develop a basic technique of renal gene therapy in which a single injection of the HGF gene makes a low, but continuous intravenous level of HGF, using an ischemic kidney model.