Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways.
Liver development is regulated by soluble factors as well as cell-cell contacts. We previously reported that oncostatin M (OSM) induced hepatic maturation in a primary culture of embryonic day 14 liver cells. While OSM expression in the liver starts in mid gestation and decreases in postnatal stages, hepatocyte growth factor (HGF) is mainly expressed in the liver in the first few days after birth. In this study, we compared the effect of OSM and HGF on the differentiation of fetal hepatic cells in vitro. Like OSM, HGF in the presence of dexamethasone induced expression of glucose-6-phosphatase, tyrosine amino transferase and carbamoyl-phosphate synthase, and accumulation of glycogen in fetal hepatic cells, although to a lesser extent than OSM. Interestingly, while both OSM and HGF up-regulated production of albumin, secretion of albumin occurred only in response to OSM. In addition, although hepatic maturation induced by OSM depends on STAT3, HGF failed to activate STAT3 and HGF-induced differentiation was independent of STAT3. These results indicate that OSM and HGF induce hepatic maturation through different signaling pathways.
Stem Cell Regulation, Kanagawa Academy of Science and Technology, Teikyo University Biotechnology Research Center 1F, Kawasaki, Japan. kamiya@stem.kast.or.jp
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Kamiya
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Kinoshita
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Miyajima
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology*; D050796:STAT3 Transcription Factor; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; C508352:Osm protein, mouse; D010455:Peptides; D050796:STAT3 Transcription Factor; D012709:Serum Albumin; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D053683:Oncostatin M; D017228:Hepatocyte Growth Factor