New therapeutic strategy to non-alcoholic liver disease targeting on autophagy

• Project/Area Number: 24390191
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: WATANEBE Sumio 順天堂大学, 医学部, 教授 (20138225)
• Co-Investigator(Kenkyū-buntansha): KENICHI Ikejima (KAZUYOSHI Kon) 順天堂大学, 医学研究科, 准教授 (20317382) ; YAMASHINA Shunhei 順天堂大学, 医学部, 准教授 (30338412) ; 今 一義 順天堂大学, 医学部, 准教授 (30398672)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2012: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
• Keywords: 脂肪性肝疾患 / オートファジー / リソソーム / カテプシン / 肝再生 / 慢性肝炎

Outline of Final Research Achievements

The lower proteolytic capability of autophagy was observed in the liver from NAFLD patients. Liver injury and hepatic inflammation correlate with autophagic dysfunction in non-alcoholic fatty liver disease (NAFLD). These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD. Impairment of autophagic proteolysis is caused by alteration of lysosomal proteins. Changes in lysosomal proteins due to hepatic steatosis might disturb autophagosomal acidification and proteolytic activity. Interestingly, autophagic dysfunction and suppression of cathepsin L expression observed in NAFLD lead to the production of anti-oxidant molecules and accelerate liver regeneration. Our results from this study may provide new approaches for the prediction of prognosis, prevention and treatment of NAFLD.

Research Products

• [Journal Article] Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease. (2014)
  • Author(s): Yuka Fukuo, Shunhei Yamashina, Hiroshi Sonoue, Atsushi Arakawa, Eisuke Nakadera, Tomonori Aoyama, Akira Uchiyama, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
  • Journal Title: Hepatology Research Volume: 未定 Issue: 9 Pages: 1026-1036
  • DOI: 10.1111/hepr.12282
  • Peer Reviewed / Open Access
• [Presentation] 肝脂肪化によるmTOR活性化を介したリソソーム酸性化障害とオートファジー機能抑制 (2015)
  • Author(s): 中寺英介、山科俊平、渡辺純夫
  • Organizer: 第101回消化器病学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2015-04-24
• [Presentation] 非アルコール性脂肪性肝疾患患者におけるオートファジー機能障害とカテプシン発現異常 (2013)
  • Author(s): 福生有華, 山科 俊平, 泉 光輔, 園上 浩司, 荒川 敦, 青山 友則, 内山 明, 今 一義, 鈴木 聡子, 池嶋 健一, 渡辺 純夫
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 京王プラザホテル