Vascular endothelial growth factor reduces Fas-mediated acute liver injury in mice.
OBJECTIVE
Fulminant hepatitis is still a fatal liver disease, and no specific treatment for it has been available. Vascular endothelial growth factor (VEGF) is the focus of attention because of its various actions. We investigated the effect of vascular endothelial growth factor (VEGF) on Fas-induced fulminant hepatic failure (FHF).


METHODS
Male Balb/c mice were treated with an intraperitoneal injection of an anti-Fas antibody (Jo-2 Ab) with or without premedication with intraperitoneally administered human recombinant VEGF.


RESULTS
The serum level of alanine aminotransferase (ALT) was up to 300 times higher that of normal mice following the Jo-2 Ab injection, and histological analysis revealed hepatic injury and massive hepatocyte apoptosis. The VEGF significantly suppressed an elevation in serum ALT levels and hepatocyte apoptosis. Immunohistochemically, VEGF-treated mice showed that Bcl-xL in hepatocytes was strongly expressed.


CONCLUSIONS
Since hepatocytes do not express VEGF receptors, we speculated that VEGF acts on sinusoidal endothelial cells (SECs) and promotes production of cytokines such as hepatocyte growth factor in SECs, resulting in reducing apoptosis through an increase expression of Bcl-xL in hepatocytes. We suggest that VEGF has a potent antiapoptotic effect on hepatocytes through cell-cell interaction between SECs and hepatocytes.
Tanaka
Yoichi
Y
Bioscience Department, Toagosei Co Ltd, Ibaraki, Japan.
Sohda
Tetsuro
T
Matsuo
Katsuhiko
K
Anan
Akira
A
Irie
Makoto
M
Takeyama
Yasuaki
Y
Iwata
Kaoru
K
Shakado
Satoshi
S
Sakisaka
Shotaro
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000906:Antibodies; D017209:Apoptosis; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017114:Liver Failure, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*