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

2014 Fiscal Year Final Research Report

• 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 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) ; KAZUYOSHI Kon 順天堂大学, 医学部, 准教授 (20317382)
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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

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.

Free Research Field

消化器病