| Project/Area Number |
25462095
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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 |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
Soejima Yuji 九州大学, 医学(系)研究科(研究院), 研究員 (30325526)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRABE Ken 群馬大学, 医学(系)研究科(研究院), 教授 (70264025)
YOSHIZUMI Tomoharu 九州大学, 医学研究院, 准教授 (80363373)
IKEGAMI Toru 九州大学, 大学病院, 助教 (80432938)
IKEDA Tetsuo 九州大学, 大学病院, 准教授 (60585701)
MAEHARA Yoshihiko 九州大学, 医学研究院, 教授 (80165662)
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝臓外科学 / オートファジー / 肝再生 / mTOR経路 / アミノ酸 / 肝幹細胞 / Atg5 / p62 |
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| Outline of Final Research Achievements |
In this study, we investigated the molecular mechanism of autophagy, with special reference to p62 and associated signaling in hepatic differentiation. Silencing of ATG5 decreased active LC3 and increased p62, which indicated inhibition of autophagy. Conversely, SQSTM1/p62 silencing impaired or delayed hepatic differentiation. Amino acid activation of mTOR signaling was enhanced by ATG5 silencing and suppressed by SQSTM1/p62 silencing. In conclusion, promoting mTOR pathway activation by amino acids is dependent on intracellular accumulation of p62, which is induced by the inhibition of autophagy and plays an important role in the hepatic differentiation of stem/progenitor cells.
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