2001 Fiscal Year Final Research Report Summary
Functional analysis of retinoic acid receptor in liver
| Project/Area Number |
10670473
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Second Department of Internal Medicine, Faculty of Medicine, Tottori University |
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Principal Investigator |
SHIOTA Goshi Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Associate Professor, 医学部, 助教授 (70263457)
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| Co-Investigator(Kenkyū-buntansha) |
KUNISADA Takahiro Department of hygiene, Faculty of Medicine, Gifu University, Associate Professor, 医学部, 教授 (30205108)
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| Project Period (FY) |
1998 – 2001
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| Keywords | retinoic acid receptor / transgenic mice / liver / steatohepatitis / fatty acid / beta oxidation / hepatocellular carcinoma |
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| Research Abstract |
We developed transgenic mice which express retinoic acid receptor dominant negative form in hepatocytes using albumin enhancer and promoter. At 3 months old, the transgenic mice (Tg) developed severe steatohepatitis. The droplet of steatosis is microvesicular, and the focal necrosis is scattered in the lobule. The growth of hepatocytes was enhanced, indicated by proliferating cell nuclear antigen expression, and the liver showed hepatomegaly. In addition to these changes, liver cell dysplasia including increased nuclear cytoplasmic ratio and abnormal staining distribution. At 12 months old, the mice developed hepatocellular carcinoma. The beta oxidation of fatty acid is impaired in mitochondria, and instead it was accelerated in peroxisome. Furthermore, omega oxidation of fatty acid in the endoplasmic reticulum was increased, resulting in production of reactive oxygen species. These data suggest that retinoic acid is essential for maintain the proper development of liver, and that retinoic acid depresses liver cancer development.
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