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.

[1]  Y. Ito,et al.  Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and ras pathways during hepatic development , 2000, Hepatology.

[2]  A. Miyajima,et al.  In vitro expansion of murine multipotential hematopoietic progenitors from the embryonic aorta-gonad-mesonephros region. , 1998, Immunity.

[3]  T. Nakamura,et al.  Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. , 1990, Biochemical and biophysical research communications.

[4]  Yoshiaki Ito,et al.  Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer , 1999, The EMBO journal.

[5]  S. Tilghman,et al.  Transcriptional control of the murine albumin/alpha-fetoprotein locus during development. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Y. Ito,et al.  Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Akira,et al.  Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway , 1994, Cell.

[8]  A. Miyajima,et al.  Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells: functional analysis of signaling molecules by retrovirus-mediated expression. , 1999, Blood.

[9]  K. Shiota,et al.  Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  T Nakamura,et al.  Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. , 1997, Biochemical and biophysical research communications.

[11]  S. Orkin.  Development of the hematopoietic system. , 1996, Current opinion in genetics & development.

[12]  C. Schindler,et al.  Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. , 1994, Science.

[13]  G. Yeoh,et al.  Enzymic differentiation in cultured foetal hepatocytes of the rat. Induction of serine dehydratase activity by dexamethasone and dibutyryl cyclic AMP. , 1983, Differentiation; research in biological diversity.

[14]  K. Zaret,et al.  Initiation of mammalian liver development from endoderm by fibroblast growth factors. , 1999, Science.

[15]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[16]  Toshikazu Nakamura,et al.  Marked increase of HGF mRNA in non-parenchymal liver cells of rats treated with hepatotoxins. , 1989, Biochemical and biophysical research communications.

[17]  G. Nolan,et al.  Efficient screening of retroviral cDNA expression libraries. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  W. Birchmeier,et al.  Hepatocyte growth factor/scatter factor (HGF/SF) signals via the STAT3/APRF transcription factor in human hepatoma cells and hepatocytes , 1997, FEBS letters.

[19]  S. Takao,et al.  Rapid and marked induction of hepatocyte growth factor during liver regeneration after ischemic or crush injury , 1992, Hepatology.

[20]  E. Houssaint.  Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. , 1980, Cell differentiation.

[21]  G. Schütz,et al.  Hepatocyte differentiation in vitro: initiation of tyrosine aminotransferase expression in cultured fetal rat hepatocytes , 1989, The Journal of cell biology.

[22]  T. Nakamura,et al.  The gene of hepatocyte growth factor is expressed in fat-storing cells of rat liver and is downregulated during cell growth and by transforming growth factor-beta. , 1992, Biochemical and biophysical research communications.

[23]  A. Miyajima,et al.  Cell density-dependent regulation of hepatic development by a gp130-independent pathway. , 2000, Biochemical and biophysical research communications.

[24]  G. Nolan,et al.  Applications of retrovirus-mediated expression cloning. , 1996, Experimental hematology.

[25]  K. Matsumoto,et al.  Developmental changes in hepatocyte growth factor mRNA and its receptor in rat liver, kidney and lung. , 1992, European journal of biochemistry.

[26]  F. Kenney,et al.  Development of tyrosine aminotransferase in perinatal rat liver: Changes in functional messenger RNA and the role of inducing hormones , 1983, Journal of cellular biochemistry.

[27]  T. Kishimoto,et al.  Gp130 and the interleukin-6 family of cytokines. , 1997, Annual review of immunology.

[28]  M. Benito,et al.  Transforming growth factor beta modulates growth and differentiation of fetal hepatocytes in primary culture. , 1995, Journal of cellular physiology.