Effects of exogenous human heparin-binding epidermal growth factor-like growth factor on DNA synthesis of hepatocytes in normal mouse liver.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been reported to stimulate DNA synthesis of the hepatocytes in culture and highly express in regenerating rat liver after partial hepatectomy. We examined mitogenic effects and activation of transcription factors caused by exogenous human HB-EGF (hHB-EGF) in mouse liver. The mean labeling index in hepatocytes of hHB-EGF-injected mice was 2.6%, a significant increase over that in saline-injected controls (under 0.01%). By exogenous hHB-EGF injection, activation of transcription factors such as nuclear factor (NF)-kappaB and activator factor (AP)-1 was observed in the liver. By Northern blot analysis, hepatocyte growth factor (HGF) gene expression in the liver was found to be induced in the hHB-EGF-injected mice. In conclusion, intravenously injected hHB-EGF showed a limited but definite effect on the DNA synthesis of hepatocytes in the mice liver. HB-EGF may serve as a hepatotrophic factor in vivo.
Kiso
S
S
Second Department of Internal Medicine, Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Osaka, Suita, 565-0871, Japan. kiso@imed2.med.osaka-u.ac.jp
Kawata
S
S
Tamura
S
S
Umeki
S
S
Ito
N
N
Tsushima
H
H
Yamada
A
A
Miyagawa
J
J
Higashiyama
S
S
Taniguchi
N
N
Matsuzawa
Y
Y
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors
C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA