title: Oncostatin M induces an acute phase response but does not modulate the growth or maturation-status of liver progenitor (oval) cells in culture.
abstract: Following acute injury, the liver regenerates through hepatocyte division. If this pathway is impaired, liver repair depends on the recruitment of adult liver progenitor (oval) cells. Mice fed a choline deficient, ethionine supplemented (CDE) diet possess substantial numbers of oval cells, which can be isolated, or examined in vivo. Oncostatin M (OSM) has been shown to induce maturation of murine fetal hepatoblasts into hepatocytes. We recently confirmed this in human fetal liver cultures. Here, we show that liver OSM expression increases in mice fed a CDE diet and CDE-derived oval cell isolates express OSM and its receptor (OSMR). Oval cell lines (PIL cells), as well as primary oval cell cultures, displayed STAT-3 phosphorylation following OSM stimulation. OSM had no effect on the growth of primary oval cells, but it was pro-apoptotic to PIL cells, suggesting that the two cell models are not directly comparable. Expression of PCNA and cyclin D1 was not affected by OSM treatment. No evidence was obtained to suggest an effect on oval cell maturation with OSM treatment. However, decreased albumin production, accompanied by increased expression of haptoglobin and fibrinogen, suggests that OSM induced an acute phase reaction in cultured oval cells.
authors.affiliation: UWA Centre for Medical Research, Western Australian Institute for Medical Research, University of Western Australia, Crawley 6009, Australia.
authors.forename: Vance B
authors.initials: VB
authors.lastname: Matthews
authors.forename: Belinda
authors.initials: B
authors.lastname: Knight
authors.forename: Janina E E
authors.initials: JE
authors.lastname: Tirnitz-Parker
authors.forename: James
authors.initials: J
authors.lastname: Boon
authors.forename: John K
authors.initials: JK
authors.lastname: Olynyk
authors.forename: George C T
authors.initials: GC
authors.lastname: Yeoh
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005001:Ethionine / Q000494:pharmacology; D005340:Fibrinogen / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006242:Haptoglobins / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000235:genetics; D053677:Receptors, Oncostatin M; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006242:Haptoglobins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D018124:Receptors, Tumor Necrosis Factor; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C464794:fibrinogen Aalpha; D053683:Oncostatin M; D005340:Fibrinogen; D002794:Choline; D005001:Ethionine