Hepatitis C as a Metabolic Disease : Pathogenesis for liver cancer and lifestyle-related diseases
| Project/Area Number |
18390214
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokyo |
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Principal Investigator |
KOIKE Kazuhiko The University of Tokyo, Graduate School of Medicine, Professor (80240703)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIE Hajime University of Tokyo, Faculty of Medicine, Associate (90332577)
YOTSUYANAGI Hiroshi University of Tokyo, Faculty of Medicine, Hospital, Lecturer (30251234)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,400,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | HCV / insulin resistance / steatosis / transgenic mouse / metabolism / proteasome activator / nuclear receptor / プロテアゾームアクテベーター / プロテアゾームアクチベーター |
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| Research Abstract |
In addition to the link with development of hepatocellular carcinoma (HCC), hepatitis C virus (HCV) infection is associated with several hepatic and extrahepatic manifestations. A role of hepatic steatosis in the pathogenesis of chronic hepatitis C has been shown, implying hepatitis C as a metabolic disease. Furthermore, recent epidemiological studies have suggested a linkage between insulin resistance and chronic HCV infection. Besides the data indicating the presence of lipid metabolism disturbance and insulin resistance in the cohort of chronic hepatitis C patients, we found a series of evidence showing the association between these two conditions and HCV infection using mice transgenic for the HCV core gene. These mice develop HCC late in life after the phase of hepatic steatosis and insulin resistance. The nonappearance of both steatosis and HCC in HCV core gene transgenic mice that are null for the proteasome activator 28g, implies a close relationship between lipid metabolism disturbance and hepatocarcinogenesis. Also, the core protein is shown to bind with retinoid X receptor (RXR)-a, resulting in the up-regulation of some lipid metabolism enzymes including cellular retinol binding protein II and acyl-CoA oxidase. In addition, the persistent activation of peroxisome proliferator activated receptor (PPAR)-a has recently been found in the liver of HCV core gene transgenic mice, yielding dramatic changes in the lipid metabolism and hepatocyte proliferation including HCC development. These results would provide a clue for further understanding of the role of lipid metabolism in pathogenesis of HCV infection including liver injury and hepatocarcinogenesis.
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Report
(3 results)
Research Products
(19 results)
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[Book] 肝癌診療マニュアル2007
Author(s)
小池和彦
Total Pages
135
Publisher
医学書院
Description
「研究成果報告書概要(和文)」より
Related Report
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