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The role of Apg-2 in liver steatosis and carcinogenesis

Research Project

Project/Area Number 15K09018
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Itoh Yoshito  京都府立医科大学, 医学(系)研究科(研究院), 教授 (70244613)

Co-Investigator(Kenkyū-buntansha) 山口 寛二  京都府立医科大学, 医学(系)研究科(研究院), 助教 (50381950)
Co-Investigator(Renkei-kenkyūsha) Fujita Jun  京都大学, 医学研究科, 教授 (50173430)
Itoh Katsuhiko  京都大学, 医学研究科, 准教授 (90281097)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsApg-2 / 分子シャペロン / 肝癌 / 細胞周期 / ユビキチン化 / 脂肪肝炎
Outline of Final Research Achievements

Heat shock proteins (HSPs) not only protect cells from the toxic effects of heat and other stresses but also have multiple housekeeping functions, such as folding and protein degradation. Apg-2 is a subfamily of Hsp110 and has been reported to be overexpressed in human hepatocellular carcinomas (HCCs). To study the role of Apg-2 in liver steatosis and carcinogenesis, we generated Apg-2 deficient mice and examined high fat diet-induced liver steatosis and diethylnitrosamine (DEN)-induced hepatocellular carcinomas (HCCs). We found that Apg-2 deficient mice exhibited less liver steatosis and DEN-induced hepatocellular carcinomas (HCCs) compared to wild-types. RNA sequence from Apg-2 deficient HCCs and in vitro study of hepatoma cell lines revealed that Apg-2 regulated cell cycle G2/M pathway-related molecules, such as CDK1/CyclinB1, and promoted HCCs proliferations. These findings indicated that Apg-2 is a potential target for the therapy of HCCs.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2017 2016 2015

All Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] 分子シャペロンApg-2をターゲットにした肝脂肪化治療戦略2017

    • Author(s)
      山口寛二、石破博、伊藤義人
    • Organizer
      第53回日本肝臓学会総会(広島)、PD2-14(追加発言)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Apg-2 plays an important role in hepatic steatosis2017

    • Author(s)
      Yamaguchi Kanji, Ishiba Hiroshi, Seko Yuya, Umemura Atsushi, Itoh Yoshito
    • Organizer
      第1回ICFL The 1st International Conference on Fatty Liver
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Apg2 is a key determinant of hepatic steatosis by regulating AMPK activity2016

    • Author(s)
      Hiroshi Ishiba, Kanji Yamaguchi, Itoh Yoshito
    • Organizer
      The Liver Meeting® 2016 第67回米国肝臓学会
    • Place of Presentation
      Boston, USA
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス脂肪肝炎における Heat shock蛋白Apg-2の役割についての検討2015

    • Author(s)
      山口寛二、石破博、伊藤義人
    • Organizer
      日本肝臓学会西部会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-10-29  

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