| Project/Area Number |
24790721
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
DAVID Brenner カリフォルニア大学サンディエゴ校, 医学部, 教授
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝組織修復機転 / 肝星細胞 / 酸化ストレス / 肝線維化 / ROS |
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| Outline of Final Research Achievements |
Hepatic stellate cells (HSCs) and Kupffer cells (KCs) have important roles in tissue-repairing process in the liver. Impaired this process caused by excessive reactive oxygen species (ROS) induces liver fibrosis and regeneration failure. NADPH oxidase (NOX) generates ROS. The NOX components form an active complex, including Rac1. Superoxide dismutase 1 (SOD1) interacts with the NOX-Rac1 complex. To clarify the interaction of SOD1-NOX-Rac1 in HSCs and KCs, we investigated liver fibrosis and regeneration using SOD1 mutant mice. Enhanced liver fibrosis and ROS production were found in SOD1 mutant mice treated by chronic carbon tetrachloride injections. In HSCs, SOD1 mutation induced excessive Rac1 activity, thereby causing enhanced NOX activation, ROS and collagen generation. Liver regeneration was not changed in SOD1 mutant mice. In conclusion, SOD1 regulates Rac1 and NOX activity in HSCs. SOD1-NOX-Rac1 interaction has a pivotal role in ROS generation of HSCs.
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