title: Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.
abstract: Oval cells of the liver participate in liver regeneration when hepatocytes are prevented from proliferating in response to liver damage. To clarify the role of oncostatin M (OSM) in the liver regeneration involving oval cells, we examined the expression of OSM and OSM-specific receptor (OSM-R) in the liver undergoing regeneration in the 2-acetylaminofluorene/partial hepatectomy model. Expression levels of OSM-R changed in correlation to the number of oval cells, and its expression was exclusively observed in oval cells. On the other hand, OSM was expressed in both oval cells and Kupffer cells. To examine the effect of OSM on the growth and differentiation of oval cells, rat oval cells (OC15-5) were incubated in conditioned medium of 293T cells expressing rat OSM cDNA. This resulted in suppression of growth, changes in morphology (microvilli and large cytoplasm with developed organelles), and expression of hepatocyte markers (albumin, tyrosine amino transferase, and tryptophan oxygenase). The effects of the conditioned medium with rat OSM were abrogated by introducing a small interfering RNA specifically targeting rat OSM-R into OC15-5 cells. These results indicate that OSM is a key mediator for inducing differentiation of OC15-5 cells into hepatocytes and suggest that the OSM/OSM-R system is pivotal in the differentiation of oval cells into hepatocytes, thereby promoting liver regeneration.
authors.affiliation: Department of Pathology, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Okaya
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitanaka
authors.forename: Nobue
authors.initials: N
authors.lastname: Kitanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Satake
authors.forename: Yuna
authors.initials: Y
authors.lastname: Kim
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Terada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Motohiko
authors.initials: M
authors.lastname: Takemura
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Terada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
mesh_terms: D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008115:Liver Regeneration; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D053683:Oncostatin M; D015388:Organelles; D010455:Peptides / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D018076:DNA, Complementary; C508351:OSM protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D053683:Oncostatin M; D015073:2-Acetylaminofluorene
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