Impact of SOX9 expressing hepatocytes on cholangiocarcinogenesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Takasu Shinji 国立医薬品食品衛生研究所, 病理部, 主任研究官 (00597891)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝臓 / ラット / SOX9 / 胆管線維症 / フラン / 胆管

Outline of Final Research Achievements

To investigate the role of SOX9-expressing hepatocytes in the cholangiocarcinogenesis, biological characteristics of SOX9-expressing hepatocytes in the furan-induced preneoplastic lesions in rat cholangiocarcinogenesis were examined. SOX9-positive hepatocytes were observed before the development of cholangiofibrosis, and number of SOX9-positive hepatocytes was increased along with the progress of the lesions. In contrast, no SOX9-positive hepatocytes were found in the non-lesional area. However, no clear association was found for the expression of bile duct epithelial cell markers in the SOX9-positive hepatocytes, suggesting that SOX9-expressing hepatocytes might be associated with the development and progression of furan-induced bile duct lesions, however, their role required further investigation.

Free Research Field

毒性病理学

Academic Significance and Societal Importance of the Research Achievements

肝内胆管癌の発生機序に係る研究は注目されており、大規模な疫学的研究やゲノム解析から慢性肝炎や肝硬変といった肝疾患が重要であることが示されているが、肝疾患から胆管癌が発生する過程の全容はよくわかっていない。本研究は動物モデルにおける胆管癌の前がん病変におけるSOX9発現肝細胞の役割を検討したものであり、今後の動物モデルを用いた胆管発がん研究に関する知見となることが期待される。