Hepatocyte growth factor protects renal epithelial cells from apoptotic cell death.
Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in renal tubular repair and regeneration following injury. Studies indicate that administration of exogenous HGF to animals stimulates renal epithelial cell DNA synthesis and accelerates recovery from acute renal failure (ARF). However, whether increased cell proliferation accounts for all of the beneficial effects of HGF in ARF is unknown. In this study, we demonstrate that HGF protects renal epithelial cells from undergoing apoptotic cell death. Treatment of renal epithelial mIMCD-3 cells with 25 microM cisplatin in the serum-free medium induced significant apoptosis, as assessed by fluorescent Dye H-33342 staining, TUNEL staining, light and electron microscopy, and DNA laddering analysis. However, constitutive expression of HGF by transfection in mIMCD-3 cells resulted in resistance to cisplatin-induced apoptotic death. The survival rate of HGF-producing C1 cells was more than 2-fold greater as compared to control, mIMCD-3 cells following treatment with 25 microM cisplatin for 2 days. These results suggest that HGF may not only activate tubular repair processes but also ameliorate the initial injury by protecting renal epithelial cells from undergoing apoptosis.
Liu
Y
Y
Department of Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence 02903, USA. Yliu@lifespan.org
Sun
A M
AM
Dworkin
L D
LD
D058186:Acute Kidney Injury; D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000473:pathology; D002470:Cell Survival; D002945:Cisplatin / Q000009:adverse effects; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D007679:Kidney Medulla / Q000166:cytology / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin