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The impact of hepatocyte apoptosis and autophagy in the process of livercarcinogenesis

Research Project

Project/Area Number 26253047
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

Takehara Tetsuo  大阪大学, 医学系研究科, 教授 (70335355)

Co-Investigator(Kenkyū-buntansha) 巽 智秀  大阪大学, 医学系研究科, 講師 (20397699)
疋田 隼人  大阪大学, 医学系研究科, 助教 (20623044)
Research Collaborator TANAKA Satoshi  大阪大学, 大学院医学系研究科
SAKANE Sadatsugu  大阪大学, 大学院医学系研究科
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2016: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2015: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2014: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywords脂肪肝 / 肝細胞 / オートファジー / アポトーシス / Rubicon / 非アルコール性脂肪性肝疾患 / 消化器内科学 / 脂肪性肝疾患
Outline of Final Research Achievements

We investigated autophagic change in the liver and the effect on liver apoptosis and lipid accumulation in NAFLD model. In liver cell lines, palmitic acid (PA) treatment suppressed autophagy with increase of Rubicon. Rubicon blockade attenuated autophagy impairment and reduced palmitate-induced apoptosis and lipid accumulation. The Rubicon increase by PA was caused by suppression of Rubicon degradation. Rubicon was also up-regulated in association with autophagy impairment in livers of mice fed a high-fat diet (HFD). Hepatocyte-specific Rubicon knockout mice showed amelioration of liver steatosis and injury as well as attenuation of autophagy impairment for four months HFD feeding. In humans, liver tissues obtained from patients with NAFLD expressed significantly higher levels of Rubicon than those without steatosis. Rubicon might be a new therapeutic target for NAFLD progression.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (20 results)

All 2017 2016 2015 2014 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice.2016

    • Author(s)
      Tanaka S, Hikita H, Tatsumi T, Sakamori R, Nozaki Y, Sakane S, Shiode Y, Nakabori T, Saito Y, Hiramatsu N, Tabata K, Kawabata T, Hamasaki M, Eguchi H, Nagano H, Yoshimori T, Takehara T.
    • Journal Title

      Hepatology

      Volume: 64 Issue: 6 Pages: 1994-2014

    • DOI

      10.1002/hep.28820

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 肝臓と脂肪組織のオートファジーによる脂肪蓄積制御2017

    • Author(s)
      坂根 貞嗣、疋田 隼人、田中 聡司、明神 悠太、塩出 悠登、野崎 泰俊、齋藤 義修、中堀 輔、小玉 尚弘、阪森 亮太郎、巽 智秀、竹原 徹郎
    • Organizer
      第1回消化器臓器間ネットワーク研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Intake of high fat diet causes suppression of hepatocyte autophagy and enhancement of adipocyte autophagy and controls fat deposition of liver and adipose tissue2017

    • Author(s)
      Sadatsugu Sakane, Hayato Hikita, Satoshi Tanaka, Yasutoshi Nozaki, Takahiro Kodama, Ryotaro Sakamori, Tomohide Tatsumi, Tsuyoshi Kawabata, Maho Hamasaki, Tamotsu Yoshimori, Tetsuo Takehara
    • Organizer
      The 8th International Symposium on Autophagy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝臓と脂肪組織のオートファジーによる肝脂肪蓄積制御2017

    • Author(s)
      坂根 貞嗣、疋田 隼人、田中 聡司、明神 悠太、塩出 悠登、野崎 泰俊、齋藤 義修、中堀 輔、小玉 尚宏、阪森 亮太郎、巽 智秀、竹原 徹郎
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Autophagic changes of both adipose tissues and the liver induced by high fat diet feeding contribute to hepatic lipid accumulation2017

    • Author(s)
      Sadatsugu Sakane, Hayato Hikita, Satoshi Tanaka, Kumiko Shirai, Naoki Mizutani, Yuta Myojin, Yuto Shiode, Yasutoshi Nozaki, Yoshinobu Saito, Tasuku Nakabori, Takahiro Kodama, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
    • Organizer
      AASLD The Liver Meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高脂肪食による脂肪組織のオートファジーの亢進が肝脂肪蓄積を増悪させる2017

    • Author(s)
      坂根貞嗣、疋田隼人、竹原徹郎
    • Organizer
      第42回日本肝臓学会西部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝細胞と脂肪細胞におけるRubiconを介した脂肪代謝の制御2016

    • Author(s)
      坂根貞嗣 竹原徹郎
    • Organizer
      第10回オートファジー研究会
    • Place of Presentation
      新潟
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脂肪酸負荷は、肝細胞Rubiconの分解遅延によりオートファジーを抑制することで、脂肪滴蓄積と肝細胞障害を増悪させる2016

    • Author(s)
      田中 聡司、 疋田 隼人、竹原 徹郎
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      千葉
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Enhanced expression of Rubicon inhibits autophagy and promotes apoptosis by increasing endoplasmic reticulum stress in nonalcoholic fatty liver disease.2015

    • Author(s)
      Satoshi Tanaka, Hayato Hikita, Sadatsugu Sakane, Yasutoshi Nozaki, Yugo Kai, Tasuku Nakabori, Yoshinobu Saito, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
    • Organizer
      The 66th Annual Meeting of the American Association for the study of Liver Disease
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhanced expression of Rubicon inhibits autophagy and promotes apoptosis by increasing endoplasmic reticulum stress in nonalcoholic fatty liver disease2015

    • Author(s)
      Satoshi Tanaka, Hayato Hikita, Tetsuo Takehara
    • Organizer
      第19回日本肝臓学会大会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非アルコール性脂肪肝炎病態形成における、オートファジー制御蛋白Rubiconの役割2015

    • Author(s)
      田中 聡司、疋田 隼人、野崎 泰俊、甲斐 優吾、牧野 祐紀、中堀 輔、齋藤 義修、阪森 亮太郎、巽 智秀、竹原 徹郎
    • Organizer
      第22回 肝細胞研究会
    • Place of Presentation
      米子
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肝細胞への脂肪酸負荷はRubicon発現増加を介してオートファジーを抑制し、肝障害を増悪させる。2015

    • Author(s)
      田中 聡司、疋田 隼人、竹原 徹郎
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] NASH病態形成におけるRubicon発現増加を介したオートファジー抑制と小胞体ストレス応答の活性化2015

    • Author(s)
      田中聡司、 疋田隼人、 竹原徹郎
    • Organizer
      第101回日本消化器病学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Increased expression of Rubicon protein by high fat diet suppresses autophagic flux and induces apoptosis by increasing endoplasmic reticulum stress in the pathogenesis of non-alcoholic fatty liver disease2014

    • Author(s)
      Satoshi Tanaka, Hayato Hikita, Yasutoshi Nozaki, Yugo Kai, Tasuku Nakabori, Yoshinobu Saito, Ryotaro Sakamori, Takuya Miyagi, Naoki Hiramatsu, Tomohide Tatsumi, Tetsuo Takehara
    • Organizer
      The 65th Annual Meeting of the American Association for the study of Liver Disease
    • Place of Presentation
      Boston, USA
    • Year and Date
      2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] ASH病態形成におけるオートファジーとアポトーシスの意義2014

    • Author(s)
      田中聡司 疋田隼人 竹原徹郎
    • Organizer
      第18回日本肝臓学会大会(JDDW2014)
    • Place of Presentation
      神戸
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脂肪肝炎におけるオートファジー制御タンパクRubicon発現上昇を介した肝細胞アポトーシスの亢進2014

    • Author(s)
      田中 聡司、疋田 隼人、野崎 泰俊、甲斐 優吾、牧野 祐紀、中堀 輔、齋藤 義修、阪森 亮太郎、宮城 琢也、巽 智秀、竹原 徹郎
    • Organizer
      第21回肝細胞研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] NASH病態形成におけるオートファジーとアポトーシスの意義2014

    • Author(s)
      田中 聡司、疋田 隼人、竹原 徹郎
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] NASH病態形成におけるオートファジーとアポトーシスの意義2014

    • Author(s)
      田中聡司、 疋田隼人、 牧野祐紀、 中堀輔、 齋藤義修、 阪森亮太郎、宮城琢也、 巽智秀、 竹原徹郎
    • Organizer
      第100回日本消化器病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
  • [Book] The オートファジー 研究者たちの集大成が見える最新ビジュアルテキスト 非アルコール性脂肪性肝疾患の病態進展における肝細胞オートファジーの影響2017

    • Author(s)
      疋田隼人、竹原徹郎
    • Publisher
      羊土社
    • ISBN
      9784758103657
    • Related Report
      2017 Annual Research Report
  • [Remarks] 脂肪肝の発症メカニズムを解明

    • URL

      http://resou.osaka-u.ac.jp/ja/research/2016/20160913_1

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2019-03-29  

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