Hepatocyte growth factor prevents lipopolysaccharide-induced hepatic sinusoidal endothelial cell injury and intrasinusoidal fibrin deposition in rats.
BACKGROUND
Acute endotoxemia is known to cause activation of Kupffer cells as well as serious injury in parenchymal and nonparenchymal cells in the liver. We have recently shown that a continuous recombinant hepatocyte growth factor (rHGF) supply prevents lipopolysaccharide (LPS)-induced liver injury in rats. As an attempt to elucidate the mechanism, here we investigate the cytoprotective effect of rHGF on sinusoidal endothelial cells (SECs) in LPS-induced liver injury in rats.


METHODS
In order to supply rHGF continuously to the liver, syngenic rat fibroblasts genetically modified to secret rat rHGF were implanted in the spleen. Fourteen days after cell implantation, we injected LPS intravenously and evaluated SEC damage histologically and blood chemically.


RESULTS
Phosphotungstic acid-hematoxylin staining revealed that rHGF treatment greatly attenuated intrasinusoidal LPS-induced fibrin deposition. The ultrastructural changes in SECs caused by LPS administration in control rats were barely detectable in rHGF-treated rats. Blood chemical analyses showed that rHGF potently suppressed the LPS-induced increase in serum hyaluronic acid and transaminase levels.


CONCLUSIONS
Our results indicate an important role for HGF in SEC protection in vivo and would suggest a novel therapeutic strategy for liver diseases with SEC injury.
Seto
S i
Si
Institute for Virus Research, Kyoto University School of Medicine, Kyoto University, 54-Shogoin Kawaracho, Sakyo-ku, Kyoto, 606-01, Japan.
Kaido
T
T
Yamaoka
S
S
Yoshikawa
A
A
Arii
S
S
Nakamura
T
T
Niwano
M
M
Imamura
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004727:Endothelium / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D005337:Fibrin / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D005337:Fibrin; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase