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 bee n reported to stimulate DNA synthesis of the hepatocytes in culture and hig hly express in regenerating rat liver after partial hepatectomy. We examine d mitogenic effects and activation of transcription factors caused by exoge nous human HB-EGF (hHB-EGF) in mouse liver. The mean labeling index in hepa tocytes 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)-kappa B an d activator factor (AP)-1 was observed in the liver. By Northern blot analy sis, hepatocyte growth factor (HGF) gene expression in the liver was found to be induced in the hHB-EGF-injected mice. In conclusion, intravenously in jected 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. (C) 1999 Academic Press.