Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.
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.
Okaya
Atsuhito
A
Department of Pathology, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, Hyogo 663-8501, Japan.
Kitanaka
Junichi
J
Kitanaka
Nobue
N
Satake
Makoto
M
Kim
Yuna
Y
Terada
Kunihiko
K
Sugiyama
Toshihiro
T
Takemura
Motohiko
M
Fujimoto
Jiro
J
Terada
Nobuyuki
N
Miyajima
Atsushi
A
Tsujimura
Tohru
T
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
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
FASEB J. 1995 Nov;9(14):1396-400
7589980
Hepatology. 2003 Nov;38(5):1095-106
14578848
Cell Prolif. 2004 Feb;37(1):1-21
14871234
Hepatology. 1998 Feb;27(2):433-45
9462642
EMBO J. 1996 Mar 1;15(5):1055-63
8605875
Cytokine Growth Factor Rev. 2000 Sep;11(3):177-83
10817961
Blood. 1999 Feb 1;93(3):804-15
9920829
Lab Invest. 1994 Apr;70(4):511-6
7513770
Life Sci. 1999;65(20):2019-30
10579456
Annu Rev Immunol. 1997;15:797-819
9143707
Semin Liver Dis. 2003 Nov;23(4):303-12
14722808
Hepatology. 2004 Mar;39(3):635-44
14999682
Mol Cell Biol. 1989 Jul;9(7):2847-53
2779549
Hepatology. 1997 Feb;25(2):329-34
9021943
Am J Pathol. 2003 Jul;163(1):3-9
12819005
Semin Cell Dev Biol. 2002 Dec;13(6):405-9
12468240
FEBS Lett. 2001 Mar 9;492(1-2):90-4
11248243
FEBS Lett. 2000 Mar 31;470(3):325-30
10745090
Cancer Res. 1956 Feb;16(2):142-8
13293655
EMBO J. 1999 Apr 15;18(8):2127-36
10205167
Blood. 1994 May 1;83(9):2619-26
7513208
Carcinogenesis. 1987 Nov;8(11):1737-40
3664968
Biochem Biophys Res Commun. 2003 Sep 19;309(2):298-304
12951049
Hepatology. 1999 Mar;29(3):670-6
10051467
Mech Dev. 2003 Jan;120(1):117-30
12490302
J Biol Chem. 1996 Dec 20;271(51):32635-43
8999038
Hepatology. 2001 Mar;33(3):738-50
11230756
Hepatology. 2000 Dec;32(6):1370-6
11093744
Hepatology. 1997 Sep;26(3):720-7
9303503
Hepatology. 2002 Jun;35(6):1351-9
12029620