Hepatocyte growth factor protects functional and histological disorders of HgCl(2)-induced acute renal failure mice.
Hepatocyte growth factor (HGF) enhances proliferation of renal epithelial cells as well as hepatocytes. HGF accelerates recovery from acute renal failure (ARF) in animal models. However, pharmacological profiles of HGF including its action mechanism has not been studied in detail. An HgCl(2)-induced ARF mouse was used in this study to evaluate the efficacy of HGF. Single administrations of recombinant human HGF or vehicle were given to ARF mice 30 min after HgCl(2) injection. Renal function was monitored by measuring serum creatinine, blood urea nitrogen and creatinine clearance. In the ARF mice, there was a deterioration of renal function biochemical parameters and histological evidence of renal damage including acute tubular necrosis of proximal tubules. These were both significantly ameliorated by a single HGF administration. The effect of HGF was noticeable in the early phase of ARF (1 day after onset) when there was no histological evidence of increased labeling indexes in renal tubular epithelial cells. Western blot analysis of the c-Met/HGF receptor showed that tyrosine phosphorylation was enhanced immediately after HGF administration indicating direct activation of renal epithelial cells. HGF prevented increase of apoptotic nuclei with DNA fragmentation in renal epithelial cells which suggests cytoprotective activity of HGF on renal epithelial cells in the ARF mice.
Yamasaki
Naoki
N
Discovery Research Laboratories II, Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Nagano
Tomokazu
T
Mori-Kudo
Ikue
I
Tsuchida
Atsushi
A
Kawamura
Takao
T
Seki
Hitoshi
H
Taiji
Mutsuo
M
Noguchi
Hiroshi
H
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002455:Cell Division / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D004202:Disinfectants; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride; D051379:Mice; D008807:Mice, Inbred BALB C
D004202:Disinfectants; D008627:Mercuric Chloride; D017228:Hepatocyte Growth Factor; D003404:Creatinine