| Abstract | BACKGROUND/AIMS: 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. 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. |
| Authors | Eduardo Homsi, Patricia Janino, Subrata K Biswas, Shinya Mizuno, Toshikazu Nakamura, Jose B Lopes de Faria
(Affiliation: Division of Nephrology, Department of Medicine, School of Medical Sciences, State University of Campinas, São Paulo, Brazil. ehomsi at aclnet.com.br)
|
| Journal | Nephron. Experimental nephrology
(Nephron Exp Nephrol)
Vol. 107
Issue 3
Pg. e95-106
( 2007)
ISSN: 1660-2129 Switzerland |
| PMID | 17940345
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
| Copyright | Copyright 2007 S. Karger AG, Basel. |
| Chemical References |
- Ccl2 protein, rat
- Chemokine CCL2
- Interleukin-1
- RNA, Messenger
- Glycerol
- Creatinine
- Hepatocyte Growth Factor
- Heme Oxygenase (Decyclizing)
- Hmox1 protein, rat
- Proto-Oncogene Proteins c-met
|
| Topics |
- Animals
- Apoptosis
(drug effects)
- Chemokine CCL2
(biosynthesis, genetics)
- Creatinine
(blood)
- Gene Expression Regulation
- Glycerol
(toxicity)
- Heme Oxygenase (Decyclizing)
(biosynthesis, genetics)
- Hepatectomy
- Hepatocyte Growth Factor
(biosynthesis, genetics, physiology)
- Interleukin-1
(biosynthesis, genetics)
- Kidney
(metabolism, physiopathology)
- Kidney Tubular Necrosis, Acute
(chemically induced, metabolism, pathology, prevention & control, surgery)
- Macrophages
(pathology)
- Proto-Oncogene Proteins c-met
(biosynthesis, genetics, physiology)
- RNA, Messenger
(biosynthesis, genetics)
- Rats
- Rats, Wistar
- Regeneration
- T-Lymphocytes
(pathology)
|
