Hepatocyte growth factor as well as vascular endothelial growth factor gene induction effectively promotes liver regeneration after hepatectomy in Solt-Farber rats.
OBJECTIVE
Hepatic oval cells play an important role in liver regeneration when proliferation of mature hepatocytes is inhibited. The aim of this study was to examine the effect of hepatocyte growth factor (HGF), or vascular endothelial growth factor (VEGF) on proliferation of oval cells in the Solt-Farber rat model.


METHODS
One hour after 70% partial hepatectomy, 2-acetyl-aminofluorene-induced damaged rats were infected intravenously with recombinant adenoviral vectors, encoding rat HGF or human VEGF, or Escherichia coli beta-galactosidase as a control.


RESULTS
The plasma HGF concentrations in the HGF-transferred rats were elevated compared with the other groups at 4 and 7 days after hepatectomy. Oval cells were confirmed by positive staining of both cytokeratin-19 and alpha-fetoprotein. Oval cells around the portal tracts in the HGF or VEGF-transferred rats increased in number compared with the control rats at 7 and 9 days after hepatectomy. The proliferating cell nuclear antigen labeling indices of oval cells and the hepatic regeneration rate after hepatectomy were significantly augmented by the HGF or VEGF treatment. Moreover, cyclin E expression was elevated in the HGF-treated rats.


CONCLUSIONS
In the Solt-Farber rat model, HGF or VEGF gene injection effectively promoted liver regeneration after hepatectomy mainly with increased proliferation of hepatic oval cells.
Oe
Hideaki
H
Department of Surgery and Surgical Basic Science, Kyoto University School of Medicine, Kyoto Japan.
Kaido
Toshimi
T
Mori
Akira
A
Onodera
Hisashi
H
Imamura
Masayuki
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000502:physiology*; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology*; D008106:Liver Cirrhosis, Experimental / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D001616:beta-Galactosidase