2004 Fiscal Year Final Research Report Summary
Regenerative medicine for liver diseases : Analysis of the development and differentiation of hepatic oval cells
Project/Area Number |
15590356
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Hyogo College of Medicine |
Principal Investigator |
TSUJIMURA Tohru Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20227408)
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Project Period (FY) |
2003 – 2004
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Keywords | oval cells / liver regeneration / Oncostatin M / Dlk |
Research Abstract |
We first examined the expression of Oncostatin M(OSM) and OSM-specific receptor(OSM-R) in the liver undergoing regeneration in the 2-acetylaminofluorene/partial hepatectomy(AAF/PH) model. OSM was expressed in both oval cells and Kupffer cells, but OSM-R was exclusively expressed in oval cells. When rat oval cells (OC15-5) were incubated in the conditioned medium of 293T cells expressing rat OSM cDNA, this resulted in suppression of growth, changes in morphology to possess microvilli and large cytoplasm with developed organells, and expression of hepatocyte markers, such as tyrosine amino transferase and tryptophan oxygenase, in OC15-5 cells. These results indicate that OSM is a key mediator for induction of the differentiation of OC15-5 cells into hepatocytes, and suggest that the OSM/OSM-R system plays a pivotal role in the differentiation of oval cells into hepatocytes, thereby promoting liver regeneration. Next, we examined the expression of Dlk in the AAF/PH model. Immunofluoresence staining analysis revealed that Dlk+ cells expressed oval cell markers, cytokeratin 19(CK19) and α-fetoprotein, indicating that Dlk is expressed in oval cells. However, Dl1k+ cells accounted for only about 20% of total CK19+ oval cells. Dlk+ cells were localized more distantly from the portal vein than Dlk- cells, and were adjacent to mature hepatocytes. Furthermore, at day 12 after PH, only 3% of Dlk+ oval cells expressed Ki67, whereas about 13% of total oval cells expressed Ki67, indicating that Dlk+ oval cells are less proliferative than Dlk- oval cells. Taken together, these results demonstrate that Dlk is expressed in a subpopulation of oval cells and that Dlk+ cells represent intermediate cells between Dlk- oval cells and mature hepatocytes.
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Research Products
(22 results)
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[Journal Article] Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.2005
Author(s)
Okaya A, Kitanaka J, Kitanaka N, Satake M, Kim Y, Terada K, Sugiyama T, Takemura M, Fujimoto J, Terada N, Miyajima A, Tsujimura T.
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Journal Title
Am J Pathol 166
Pages: 709-719
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells.2004
Author(s)
Okamoto T, Yamada N, Tsujimura T, Sugihara A, Nishizawa Y, Ueda H, Kashiwamura S, Tsutsui H, Futani H, Maruo S, Okamura H, Terada N.
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Journal Title
J Interferon Cytokine Res 24
Pages: 161-167
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Necessity of tyrosine 719 and phosphatidylinositol 3'-kinase-mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the D814V mutation.2003
Author(s)
Hashimoto K, Matsumura I, Tsujimura T, Kim D-K, Ogihara H, Ikeda H, Ueda S, Mizuki M, Sugawara H, Shibayama H, Kitamura Y, Kanakura Y.
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Journal Title
Blood 101
Pages: 1094-1102
Description
「研究成果報告書概要(欧文)」より
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