Establishment of new mouse models for investigating the effect of fatty liver on intrahepatic bile duct cancer development

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Gifu University
• Principal Investigator: Shirakami Yohei 岐阜大学, 医学部附属病院, 助教 (50632816)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝内胆管癌 / 脂肪肝 / 肥満

Outline of Final Research Achievements

This study was conducted to establish a novel animal model for intrahepatic cholangiocarcinoma. The liver of obese db/db mice administered the colorectal carcinogen azoxymethane exhibited obesity-induced fatty liver, proliferative changes and dysplasia of the small bile ducts, as well as cholangiocarcinoma. Gene expressions related to inflammatory cytokines and IGF signaling pathway were elevated in the liver of db/db mice with bile duct lesions, suggesting that chronic inflammation caused by the development of hepatic steatosis promoted proliferative changes in bile ducts and intrahepatic cholangiocarcinoma.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

生活習慣の変化から肥満人口が増加しているが、肥満の存在によりさまざまながんの発生率が上昇することが知られている。本研究結果は、肥満に伴う肝脂肪化の進展による慢性炎症が、肝内胆管癌の発生に関与することを示唆するとともに、肥満を呈するマウスを用いた肝内胆管癌モデルがヒト胆管癌の病態を反映した新規動物モデルとして有用であり、発癌および進展機序の解明や治療法の開発に寄与する可能性を示している。