Mutual plasticity between hepatocytes and bile ductular cells in ductular reaction - its significance and therapeutic implications

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390092
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Nishikawa Yuji 旭川医科大学, 医学部, 教授 (90208166)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Masahiro 旭川医科大学, 医学部, 助教 (30431399) ; FUJII Kiyonaga 旭川医科大学, 医学部, 助教 (10278327) ; OOSHIO Takako 旭川医科大学, 医学部, 助教 (80723238)
• Co-Investigator(Renkei-kenkyūsha): MARUYAMA Hiroki 新潟大学, 大学院医歯薬総合研究科, 教授 (10293218)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 肝細胞 / 胆管上皮細胞 / 細胆管反応 / 分化転換 / 肝傷害 / 肝線維化

Outline of Final Research Achievements

We examined the cellular mechanisms of ductular reaction associated with chronic liver injuries by hepatocyte lineage tracing experiments in vivo. Our results demonstrated that hepatocytes could transdifferentiate into ductular cells within the damaged areas incited by various chronic injurious stimuli. We also showed that, in centrilobular liver injuries, duct/ductular structures in the periportal areas proliferated and migrated to the injured areas and established the connections with hepatocyte-deribed ductules. Such remodeling of existing bile duct/ductular cells and transdifferentiated hepatocytes has not been described. These findings, together with various in vitro and in vivo experiments performed in this study, would provide useful information for the development of novel therapeutics for chronic liver diseases.

Free Research Field

病理学