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 fi;st 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 upregulated 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. (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.