| Project/Area Number |
25461000
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyushu University |
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Principal Investigator |
Kato Masaki 九州大学, 大学病院, 助教 (60444808)
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| Co-Investigator(Kenkyū-buntansha) |
Kotoh Kazuhiro 九州大学, 大学病院, 講師 (80289579)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 低酸素 / 肝線維化 / 肝発癌 / 肝星細胞 / 末梢血単核球 / indian hedgehog / adrenomedullin / p21 / hedgehog / HO-1 / VEGFA / VEGFR2 / 慢性肝炎 / 肝硬変 / 類洞血流 / 定量的PCR |
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| Outline of Final Research Achievements |
Intrahepatic hypoxia may enhance liver fibrosis and stimulate hepatic carcinogenesis in chronic liver disease. In thioacetamide induced rat chronic liver injury model, we observed the presence of hypoxia in liver parenchyma in the early period of injury and the activation of hepatic stellate cell, probably due to the down-regulation of Indian hedgehog. Then we analyzed the mRNA expression levels of hypoxia responsible genes in the peripheral blood mononuclear cells isolated from the patients with chronic liver disease. We observed the enhanced expressions of hypoxia response genes (HIF1, HO-1), and angiogenesis regulating genes (VEGFA, Adrenomedullin), which may suggest the presence of intrahepatic hypoxia. Corresponding expression of p21, a gene sensitive to DNA injury, was also elevated, suggesting the intrahepatic hypoxia may be involved in the DNA injury, leading to the increase of the risk of liver cancer.
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