Hepatocyte growth factor inhibits apoptosis after ischemic renal injury in rats

Abstract

Several studies have determined that growth factors, including hepatocyte growth factor (HGF), have a crucial role in the regenerative process of renal tubules after ischemic or toxic insult. Recent research has ascertained that as well as necrotic cell death, there is evidence of apoptosis after an acute renal injury. We attempted to determine the effect of HGF on apoptosis after ischemic renal injury in rats. We administered HGF or vehicle to 12 rats after ischemic insult and compared them with 6 sham-operated controls. Rats were killed at 48 hours, and histopathologic assessments were performed on the renal tissue. The microscale autoradiographic method was used for qualitative analysis of DNA fragmentation. This method was chosen over the widely used ethidium bromide[ndash ]staining method because it increases the sensitivity of detection of apoptotic DNA. Terminal deoxynucleotidyl transferase[ndash ]mediated deoxyuridine triphosphate-biotin nick end labeling histopathologic staining was used to identify apoptosis in situ. Apoptotic changes were clearly shown by electron microscopy in vehicle-treated animals. Despite showing profound evidence of tubular necrosis, apoptotic changes were markedly reduced in HGF-treated animals compared with vehicle-treated animals. DNA-laddering analysis further confirmed the antiapoptotic effect of HGF. To our knowledge, this is the first in vivo illustration of the inhibitory activity of a growth factor on apoptosis in the setting of tubular necrosis. The role of apoptosis in the setting of acute renal failure has not been elucidated; thus, additional research is necessary to determine the significance of these findings. [copy ] 2001 by the National Kidney Foundation, Inc.