Cell density-dependent regulation of hepatic development by a gp130-independent pathway.
We previously demonstrated that oncostatin M (OSM) promotes hepatic development in concert with glucocorticoid. The livers from mice deficient for gp130, a signaling subunit of the OSM receptor, displayed reduced expression of hepatic differentiation marker and defective glycogenic function. However, these phenotypes were not completely abolished in gp130(-/-) mice, suggesting that there is an alternative pathway regulating hepatic development in vivo. To test this possibility, we cultured gp130(-/-) fetal hepatic cells and investigated a signal that induces hepatic differentiation. When hepatocytes were forced to interact with each other by inoculating cells at high densities, hepatic differentiation was induced even in the absence of gp130. Moreover, cells stimulated with OSM and/or cultured at a high density possess many other metabolic functions. These observations suggest that fetal hepatic cells acquire multiple characteristics of differentiated hepatocytes in response to the signals generated by cell-cell contacts as well as by OSM.
Kojima
N
N
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan.
Kinoshita
T
T
Kamiya
A
A
Nakamura
K
K
Nakashima
K
K
Taga
T
T
Miyajima
A
A
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000378:metabolism; D002450:Cell Communication; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D053677:Receptors, Oncostatin M; D050796:STAT3 Transcription Factor; D012709:Serum Albumin / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; C494200:Il6st protein, mouse; D008112:Liver Glycogen; D008562:Membrane Glycoproteins; C508352:Osm protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D050796:STAT3 Transcription Factor; D012709:Serum Albumin; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D000641:Ammonia