Attenuation of glycerol-induced acute kidney injury by previous partial hepatectomy: Role of hepatocyte growth factor/c-met axis in tubular protection

Abstract

Background/Aims: Previous partial hepatectomy (HPTX) can attenuate glycerol-induced acute kidney injury (GlyAKI). The aim of this study was to explore the pathophysiological mechanisms and the role of hepatocyte growth factor (HGF) in kidney protection. Methods: Rats were subjected to HPTX 24 h before glycerol administration. Renal function, acute tubular necrosis, apoptosis, leukocyte infiltration, and the expression of HGF, c-met, monocyte chemoattractant protein-1, interleukin-1 beta, and heme oxygenase-1 were evaluated 24 h after glycerol injection. The regenerative response was analyzed from 6 to 72 h after glycerol injection (BrdU incorporation). In a separate series of experiments, Gly-AKI+HPTX rats were treated with antiHGF antibody. Results: Gly-AKI+ HPTX rats showed an increased expression of renal HGF and c-met as well as an improved creatinine clearance and reduced acute tubular necrosis and apoptosis, cytokine expression, and leukocyte infiltration. The regenerative response was less intense 24 and 72 h after glycerol administration in this group. The anti-HGF treatment disclosed an important role of HGF in the reduction of tubular injury, particularly apoptosis. Overexpression of heme oxygenase-1 was observed in Gly-AKI+ HPTX rats, but was not associated with HPTX-induced renal protection. Conclusion: We conclude that Gly-AKI+ HPTX rats have a reduced susceptibility to renal injury instead of an increased regenerative response and that endogenous HGF overexpression is responsible for suppression of tubular apoptosis. Copyright (C) 2007 S. Karger AG, Basel.