HEPATOCYTE GROWTH-FACTOR PROTECTS RENAL EPITHELIAL-CELLS FROM APOPTOTIC CELL-DEATH

Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an e ssential role in renal tubular repair and regeneration following injur y. Studies indicate that administration of exogenous HGF to animals st imulates renal epithelial cell DNA synthesis and accelerates recovery from acute renal failure (ARF). However, whether increased cell prolif eration accounts for all of the beneficial effects of HGF in ARF is un known. In this study, we demonstrate that HGF protects renal epithelia l cells from undergoing apoptotic cell death. Treatment of renal epith elial mIMCD-3 cells with 25 mu M cisplatin in the serum-free medium in duced significant apoptosis, as assessed by fluorescent Dye H-33342 st aining, TUNEL staining, light and electron microscopy, and DNA ladderi ng analysis. However, constitutive expression of HGF by transfection i n mIMCD-3 cells resulted in resistance to cisplatin-induced apoptotic death. The survival rate of HGF-producing C1 cells was more than 8-fol d greater as compared to control, mIMCD-3 cells following treatment wi th 25 mu M cisplatin for 2 days. These results suggest that HGF may no t only activate tubular repair processes but also ameliorate the initi al injury by protecting renal epithelial cells from undergoing apoptos is. (C) 1998 Academic Press.