Effects of growth factors on the growth and differentiation of mouse fetal liver epithelial cells in primary cultures.

J Gastroenterol Hepatol

Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 B5 Yamadaoka, Suita, Osaka 565-0871, Japan.

Published: June 2005

Background And Aims: Growth factors (GF) are thought to affect the growth and differentiation of hepatocytes during liver development. However, in the midfetal liver, little is known concerning the role of GF.

Methods: The DNA synthesis of fetal liver epithelial cells (FLEC) in monolayer culture and the liver-specific gene expressions of FLEC in 3-D culture were examined in medium supplemented with various GF.

Results: DNA synthesis of FLEC was higher than that of adult hepatocytes without GF, and was increased by hepatocyte growth factor (HGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). However, FLEC responded less to GF in terms of DNA synthesis than adult hepatocytes. The liver-specific gene expressions were increased in the presence of HGF, HB-EGF, bFGF and EGF. In embryonic day (E) 13.5 FLEC, this increase was more apparent in the presence of HB-EGF, whereas in E14.5 FLEC, it was more apparent in the presence of HGF.

Conclusions: Hepatocyte growth factor, HB-EGF, bFGF, EGF and TGF-alpha increased DNA synthesis of FLEC. HGF, HB-EGF, bFGF and EGF led to an increase in liver-specific gene expressions; and their effects on differentiation differ as a function of gestation age.

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http://dx.doi.org/10.1111/j.1440-1746.2005.03812.xDOI Listing

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