Central role of autophagy in the pathogenesis of gastrointestinal and hepatic diseases.

• Project/Area Number: 21390234
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: WATANABE Sumio 順天堂大学, 医学部, 教授 (20138225)
• Co-Investigator(Kenkyū-buntansha): IKEJIMA Kenichi 順天堂大学, 医学研究科, 准教授 (20317382) ; YAMASHINA Shyunhei 順天堂大学, 医学部, 准教授 (30338412) ; KON Yoshikazu 順天堂大学, 医学部, 准教授 (30398672)
• Co-Investigator(Renkei-kenkyūsha): UENO Takashi 順天堂大学, 医学部, 准教授 (10053373)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2009: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
• Keywords: オートファジー / 肝障害 / 肝再生 / 細胞死 / 炎症 / 脂肪性肝炎 / 酸化ストレス / エイコサペンタエン酸 / インスリン抵抗性 / ミトコンドリア / リソソーム / 潰瘍性大腸炎

Research Abstract

We found that hepatic steatosis suppresses autophagic function in both hepatocytes and Kupffer cells. Autophagy-deficiency enhances hepatic inflammation, cell death and carcinogenesis. Moreover, loss of autophagy enhances colitis but not carcinogenesis. These findings indicate that suppression of autophagy plays a pivotal role on development of various gastrointestinal and hepatic diseases.

Research Products

• [Journal Article] Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells (2011)
  • Author(s): Inami Y, Waguri S, Sakamoto A, Kouno T, Nakada K, Hino O, Watanabe S, Ando J, Iwadate M, Yamamoto M, Lee MS, Tanaka K, Komats M
  • Journal Title: J Cell Biol Volume: 193(2) Pages: 275-275
  • Peer Reviewed
• [Journal Article] Loss of autophagy promotes murine acetaminophen hepatotoxicity (2011)
  • Author(s): Igusa Y, Yamashina S, Izumi K, Inami Y, Fukada H, Komatsu M, Tanaka K, Ikejima K
  • Journal Title: Watanabe S J Gastroenterol
  • NAID: 10030650144
  • Peer Reviewed
• [Journal Article] Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression (2011)
  • Author(s): Inami Y, Yamashina S, Izumi K, Ueno T, Tanida I, Ikejima K, Watanabe S
  • Journal Title: Biochem Biophys Res Commun Volume: 412(4) Pages: 618-618
  • Peer Reviewed
• [Journal Article] Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells (2011)
  • Author(s): Inami Y, Waguri S, Sakamoto A, Kouno T, Nakada K, Hino O, Watanabe S, Ando J, Iwadate M, Yamamoto M, Lee MS, Tanaka K, Komatsu M
  • Journal Title: J Cell Biol Volume: 193 Issue: 2 Pages: 275-284
  • DOI: 10.1083/jcb.201102031
  • Peer Reviewed
• [Journal Article] Loss of autophagy promotes murine acetaminophen hepatotoxicity (2011)
  • Author(s): Igusa Y, Yamashina S, et al
  • Journal Title: Journal of Gastroenterology Volume: 47 Issue: 4 Pages: 433-443
  • DOI: 10.1007/s00535-011-0500-0
  • Peer Reviewed
• [Journal Article] Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression (2011)
  • Author(s): Inami Y, Yamashina S, et al
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 412 Issue: 4 Pages: 618-25
  • DOI: 10.1016/j.bbrc.2011.08.012
  • Peer Reviewed
• [Presentation] 肝細胞内脂肪滴蓄積とオートファジー機能障害 (2011)
  • Author(s): 山科俊平、稲見義宏、今一義、池嶋健一、渡辺純夫
  • Organizer: 第47回日本肝臓学会総会ワークショップ
  • Place of Presentation: 東京都ホテルグランパシフィック
  • Year and Date: 2011-06-02
• [Presentation] Loss of autophagy enhances the sensitization of Kupffer cells to endo toxin (2010)
  • Author(s): Hiroo Fukada, Shunhei Yamashina, Kousuke Izumi, Yoshihiro Inami, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
  • Organizer: The American association for the study of liver diseases 61th annual meeting and postgraduate course# 1971
  • Place of Presentation: 米国ボストンHynes convention center
  • Year and Date: 2010-11-03
• [Presentation] 肝細胞内脂肪滴によるオートファジー機能障害と酸化ストレス (2010)
  • Author(s): 稲見義宏、山科俊平、渡辺純夫
  • Organizer: 第18回日本消化器関連学会週間
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-10-14
• [Presentation] 肥満モデルにおけるオートファジーを介した蛋白分解機能の変化 (2010)
  • Author(s): 稲見義宏、山科俊平、渡辺純夫
  • Organizer: 第46回日本肝臓学会総会パネルディスカッション
  • Place of Presentation: 山形県山形テルサホール
  • Year and Date: 2010-05-28
• [Presentation] 肥満モデルにおけるオートファジーを介した蛋白分解機能の変化 (2010)
  • Author(s): 稲見義宏、山科俊平、渡辺純夫
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: ホテルメトロポリタン山形
  • Year and Date: 2010-05-27
• [Presentation] Lipid accumulation inhibits induction of autophagy in the mouse liver (2009)
  • Author(s): Yoshihiro Inami, Shunhei Yamashina, Kousuke Izumi, Hiroo Fukada, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
  • Organizer: The American association for the study of liver diseases 60th annual meeting and postgraduate course# 1875
  • Place of Presentation: 日米国ボストンHynes convention center
  • Year and Date: 2009-11-03
• [Presentation] Lipid accumulation inhibits induction of autophagy in the mouse liver (2009)
  • Author(s): 稲見義宏
  • Organizer: 米国肝臓病学会
  • Place of Presentation: 米国ボストン
  • Year and Date: 2009-11-03