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(American Journal of Pathology. 2005;166:709-719.)
© 2005 American Society for Investigative Pathology

Oncostatin M Inhibits Proliferation of Rat Oval Cells, OC15-5, Inducing Differentiation into Hepatocytes

Atsuhito Okaya*{dagger}, Junichi Kitanaka{ddagger}, Nobue Kitanaka{ddagger}, Makoto Satake*{dagger}, Yuna Kim*, Kunihiko Terada§, Toshihiro Sugiyama§, Motohiko Takemura{ddagger}, Jiro Fujimoto{dagger}, Nobuyuki Terada*, Atsushi Miyajima and Tohru Tsujimura*

From the Departments of Pathology,* Surgery,{dagger} and Pharmacology,{ddagger} Hyogo College of Medicine, Hyogo; the Department of Biochemistry,§ Akita University School of Medicine, Akita; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan

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.




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