Assessment of in vitro growth potential of hepatocytes expressing hepatocyte growth factor in an autocrine fashion.
We recently developed transgenic mice expressing hepatocyte growth factor (HGF) specific to hepatocytes. Hepatocytes of HGF transgenic mice showed a 2-fold increase of DNA labeling indices in vivo compared with those of wild type mice. To assess in vitro growth potential of hepatocytes from HGF transgenic mice, we studied the effects of epidermal growth factor (EGF), insulin or transforming growth factor beta (TGF beta) on DNA synthesis of hepatocytes derived from HGF transgenic or wild type mice, respectively. We found that DNA synthesis of hepatocytes from HGF transgenic mice was significantly enhanced, compared with that from wild type mice, respectively, and that its effect was additive with EGF or insulin. Further, growth-inhibitory effects of TGF beta on hepatocytes was greatly depressed in transgenic mice-derived hepatocytes, compared with that in wild type hepatocytes. These data suggest that the autocrine action of HGF is a potent stimulus for hepatocyte growth, and stress its importance as regulator of liver regeneration.
Shiota
G
G
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Kawasaki
H
H
Nakamura
T
T
Schmidt
E V
EV
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D007328:Insulin; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA