HEPATOCYTE GROWTH-FACTOR PREVENTS ACUTE-RENAL-FAILURE AND ACCELERATESRENAL REGENERATION IN MICE

Although acute renal failure is encountered with administration of nep hrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepa tocyte growth factor (HGF) is a potent hepatotropic factor for liver r egeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cell s. Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caus ed by administration of cisplatin, a widely used antitumor drug, or Hg Cl2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction. Moreover, exogenous HGF stimulated DNA synthesis o f renal tubular cells after renal injuries caused by HgCl2 administrat ion and unilateral nephrectomy and induced reconstruction of the norma l renal tissue structure in vivo. Taken together with our previous fin ding that expression of HGF was rapidly induced after renal injuries, these results allow us to conclude that HGF may be the long-sought ren otropic factor for renal regeneration and may prove to be effective tr eatment for patients with renal dysfunction, especially that caused by cisplatin.