title: Attenuation of glycerol-induced acute kidney injury by previous partial hepatectomy: role of hepatocyte growth factor/c-met axis in tubular protection.
abstract: OBJECTIVE
  Previous partial hepatectomy (HPTX) can attenuate glycerol-induced acute kidney injury (Gly-AKI). 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-1beta, 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 anti-HGF 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, School of Medical Sciences, State University of Campinas, São Paulo, Brazil. ehomsi@aclnet.com.br
authors.forename: Eduardo
authors.initials: E
authors.lastname: Homsi
authors.forename: Patricia
authors.initials: P
authors.lastname: Janino
authors.forename: Subrata K
authors.initials: SK
authors.lastname: Biswas
authors.forename: Shinya
authors.initials: S
authors.lastname: Mizuno
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Jose B
authors.initials: JB
authors.lastname: Lopes de Faria
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D003404:Creatinine / Q000097:blood; D005786:Gene Expression Regulation; D005990:Glycerol / Q000633:toxicity*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D008264:Macrophages / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007375:Interleukin-1; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D003404:Creatinine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D019859:Proto-Oncogene Proteins c-met; D005990:Glycerol