The role of nuclear receptor CAR in hepatic progenitor cell-mediated bile duct epithelial cell proliferation, bile duct formation and regeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K09453
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Gunma University
• Principal Investigator: Yamazaki Yuichi 群馬大学, 医学部附属病院, 助教 (00582404)
• Co-Investigator(Kenkyū-buntansha): 柿崎 暁 群馬大学, 大学院医学系研究科, 講師 (80344935)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 核内受容体CAR / 肝前駆細胞 / 胆管上皮細胞増殖 / 胆管形成 / 胆管再生

Outline of Final Research Achievements

The aim of this study was to investigate the role of nuclear receptor CAR in hepatic progenitor cell-mediated bile duct epithelial cell proliferation. Immunostaining and flow cytometry showed that CAR KO mice had decreased numbers of bile duct epithelial cells compared to wild-type mice, but we were unable to clarify differences in the dendritic three-dimensional structure of intrahepatic bile ducts. We reported that CAR may be involved in bile duct epithelial cell proliferation mediated by hepatic progenitor cells in liver injury model, but in this study, we could not confirm the involvement of CAR in bile duct formation, regeneration, and the three-dimensional structure of intrahepatic bile ducts.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

肝前駆細胞を介した胆管上皮細胞増殖を誘導する肝障害モデルでは、核内レセプターCARの肝障害、胆管上皮細胞増殖への関与が報告されている。肝障害のない状態での肝前駆細胞を介した胆管上皮細胞増殖、胆管形成、再生におけるCARの関与を検討した。免疫組織染色、フローサイトメトリー法、肝内胆管の樹状三次元構造を可視化して検討したが、CARの関与は明らかでなかった。肝障害のない状態でのCARの関与の有無を検討したことは、肝障害モデルを含めた肝前駆細胞を介した胆管上皮細胞増殖、胆管形成、再生及びCARの病態生理を考えるうえで意義があったと考える。