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Molecular mechanism of autophagy during differentiation and induction of hepatic stem cells in liver injury and regeneration

Research Project

Project/Area Number 25462095
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

Soejima Yuji  九州大学, 医学(系)研究科(研究院), 研究員 (30325526)

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)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
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)
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
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.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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