Effects of growth factors on the growth and differentiation of mouse fetal liver epithelial cells in primary cultures.
OBJECTIVE
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.
Kawasaki
Takako
T
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 B5 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tamura
Shinji
S
Kiso
Shinichi
S
Doi
Yoshinori
Y
Yoshida
Yuichi
Y
Kamada
Yoshihiro
Y
Saeki
Ayuko
A
Saji
Yukiko
Y
Matsuzawa
Yuji
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy
D006133:Growth Substances; D004247:DNA