Continuous hepatocyte apoptosis induces HCC in the liver

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: HIKITA Hayato 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (20623044)
• Co-Investigator(Kenkyū-buntansha): TATSUMI Tomohide 大阪大学, 大学院医学系研究科, 助教 (20397699)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝細胞死 / 肝細胞癌

Outline of Final Research Achievements

Activation of the mitochondrial pathway of apoptosis increased oxidative stress in hepatocytes and tBid released ROS from mitochondria. Hepatocyte-specific Bcl-xL or Mcl-1 KO mice coursed continuous hepatocyte apoptosis with increase of reciprocal regeneration, fibrosis, inflammation cytokines and oxidative stress. They also developed liver tumorgenesis. Bak, Bax or Bid deficiency attenuated hepatocytes apoptosis, oxidative stress and tumorigenesis rate in Mcl-1KO mice. An antioxidant did not affect the levels of hepatocyte apoptosis, reciprocal regeneration, fibrosis and inflammation cytokines but attenuated oxidative stress and decreased incidence rates of HCC. These results indicated that continuous hepatocyte apoptosis induced accumulation of oxidative stress in their liver which resulted in liver carcinogenesis. This study supports a concept that antioxidant therapy may be useful for suppressing liver carcinogenesis in patients with chronic liver disease.

Free Research Field

消化器病学