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From the First Department of Internal Medicine,*
Faculty
of Medicine, University of Tokyo, Tokyo; and the Third Department of
Internal Medicine,
Saitama Medical School,
Saitama, Japan
Both transforming growth factor-
(TGF-) and hepatocyte growth
factor (HGF) induce DNA synthesis in hepatocytes in
vitro and in vivo. Hepatic and circulating
levels of HGF have been reported to increase before an increase in
TGF- levels in several rat models of liver regeneration. In
addition, serum TGF- levels increase after an increase in
serum HGF levels in patients with either partial hepatectomy or acute
hepatitis. In this study, we investigate the significance of
TGF- in hepatocyte proliferation. TGF- contents and DNA synthesis
in cultured rat hepatocytes increased 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- mRNA oligonucleotide.
Furthermore, the addition of anti-TGF- rabbit IgG suppressed
the increase in DNA synthesis. When the anti-TGF- antibody was
administered to rats after partial hepatectomy, the number of
mitotic hepatocytes was reduced in comparison to rats treated with
normal rabbit IgG. These results were observed even though hepatic HGF
levels were increased equally in rats given either anti-TGF-
antibody or normal rabbit IgG. Our results suggest that HGF stimulates
TGF- production in rat hepatocytes, and that the mitogenic
activity of HGF depends on endogenous TGF- activity.
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