1990 Fiscal Year Final Research Report Summary
Study of liver specific gene expression in primary cultured hepatocytes for establishing hybrid Artificial liver
Project/Area Number |
01570738
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Digestive surgery
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Research Institution | Chiba University School of Medicine |
Principal Investigator |
HAYASHI Haruyuki Chiba Univ. Sch. Med. Assistant, 医学部, 助手 (00218588)
|
Co-Investigator(Kenkyū-buntansha) |
TABATA Yoichiro Chiba Univ. Sch. Med. Assistant, 医学部, 助手 (30163653)
TAIRA Masanori Chiba Univ. Sch. Med. assistant, 医学部, 助手 (60150083)
|
Project Period (FY) |
1989 – 1990
|
Keywords | Hybrid Artificial Liver / liver specific gene / c-myc / primary Cultured Hepatocytes / Gene Expression |
Research Abstract |
It is essential for a hybrid artificial liver to establish a culture system which maintains liver-specific function. Expression of liver-specific genes (albumin and ornithine transcarbamylase) in rat hepatocytes in primary culture was examined by Northern blot hybridization. The expression was significantly decreased within 24 hours after starting the culture and the low level of the expression sustained under various culture conditions. In contrast, growth related gene expression (oncogenes and ornithine decarboxylase) increased within 48 hours after starting the culture. These results indicate that the depression of liver specific gene expression in the primary culture is de-differentiation process which is closely linked with cell proliferation. To further examine the mechanism of growth stimulation in the cultured hepatocytes, signal transduction pathways leading to c-myc expression were analyzed. We found that inhibition of phosphatidylinositol turnover significantly attenuated the c-myc expression in a dose-dependent manner and that supplement of intracellular Ca^<2+> reversed this effect. It was thereby suggested that accelerated phosphatidylinositol turnover and Ca^<2+> mobilization maintains constant expression of c-myc in the cultured hepatocytes. Further analysis of persisting growth stimulation in cultured hepatocytes is required to establish growth arrested cells which may maintain the liver specific functions.
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Research Products
(4 results)