T. Tomiya et al., The mitogenic activity of hepatocyte growth factor on rat hepatocytes is dependent upon endogenous transforming growth factor-alpha, AM J PATH, 157(5), 2000, pp. 1693-1701
Citations number
78
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Both transforming growth factor-alpha (TGF-alpha) and hepatocyte growth fac
tor (HGF) induce DNA synthesis in hepatocytes in vitro and in vivo. Hepatic
and circulating levels of HGF have been reported to Increase before an inc
rease in TGF-alpha levels in several rat models of liver regeneration. In a
ddition, serum TGF-alpha levels increase after an increase in serum HGF lev
els in patients with either partial hepatectomy or acute hepatitis, In this
study, we investigate the significance of TGF-alpha in hepatocyte prolifer
ation. TGF-alpha contents and DNA synthesis in cultured rat hepatocytes inc
reased in response to HGF addition to the culture medium in a dose-related
manner. These increases were suppressed by the addition of anti-sense TGF-a
lpha mRNA oligonucleotide. Furthermore, the addition of anti-TGF-alpha rabb
it IgG suppressed the increase in DNA synthesis. When the anti-TGF-alpha an
tibody was administered to rats after partial, hepatectomy, the number of m
itotic hepatocytes was reduced In comparison to rats treated with normal ra
bbit IgG. These results were observed even though hepatic HGF levels were i
ncreased equally in rats given either anti-TGF-alpha antibody or normal rab
bit IgG. Our results suggest that HGF stimulates TGF-alpha production in ra
t hepatocytes, and that the mitogenic activity of HGF depends on endogenous
TGF-alpha activity.