Novel therapeutic approaches for biliary cystogenesis of Caroli's disease with congenital hepatic fibrosis based on the analysis of microRNAs

• Project/Area Number: 15K08342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kanazawa University
• Principal Investigator: Sato Yasunori 金沢大学, 医学系, 准教授 (30324073)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝臓 / 胆道 / 分子病理 / 人体病理学 / 胆管細胞 / 肝線維嚢胞性疾患

Outline of Final Research Achievements

The polycystic kidney (PCK) rat was analyzed as an animal model of Caroli’s disease with congenital hepatic fibrosis in this study. In vitro experiments revelated that PCK cholangiocytes were characterized by the reduced expression of miR-125b-1-3p, and the resultant overexpression of Smoothened and the Hedgehog signaling activation led to overgrowth of PCK cholangiocytes. In vivo administration of Smoothened antagonist (cyclopamine) significantly reduced the severity of bile duct dilatation and kidney cyst formation of the PCK rats. These results indicate that inhibition of the Hedgehog signaling represents a potential target of therapy for Caroli’s disease with congenital hepatic fibrosis.

Research Products

• [Presentation] Hedgehogシグナルの阻害はCaroli病動物モデルPCKラットの肝内胆管拡張を抑制する (2018)
  • Author(s): 佐藤保則，山村美奈子，佐々木素子，原田憲一
  • Organizer: 第54回日本肝臓学会総会