PUBLICATION
Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model
- Authors
- Lee, S., Memon, A., Chae, S.C., Shin, D., Choi, T.Y.
- ID
- ZDB-PUB-240116-2
- Date
- 2024
- Source
- Biochemical and Biophysical Research Communications 696: 149512149512 (Journal)
- Registered Authors
- Shin, Donghun
- Keywords
- Epcam, Intrahepatic duct, Liver progenitor cells (LPCs), Liver regeneration, Primary biliary cholangitis (PBC), Zebrafish
- MeSH Terms
-
- Animals
- Bile Ducts, Intrahepatic/metabolism
- Cholangitis*/pathology
- Epithelial Cell Adhesion Molecule/genetics
- Epithelial Cell Adhesion Molecule/metabolism
- Epithelial Cells/metabolism
- Hepatocytes/metabolism
- Humans
- Liver/metabolism
- Liver Regeneration
- Zebrafish*
- PubMed
- 38224664 Full text @ Biochem. Biophys. Res. Commun.
Citation
Lee, S., Memon, A., Chae, S.C., Shin, D., Choi, T.Y. (2024) Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model. Biochemical and Biophysical Research Communications. 696:149512149512.
Abstract
Epithelial cell adhesion molecules (EpCAMs) have been identified as surface markers of proliferating ductal cells, which are referred to as liver progenitor cells (LPCs), during liver regeneration and correspond to malignancies. These cells can differentiate into hepatocytes and biliary epithelial cells (BECs) in vitro. EpCAM-positive LPCs are involved in liver regeneration following severe liver injury; however, the in vivo function of EpCAMs in the regenerating liver remains unclear. In the present study, we used a zebrafish model of LPC-driven liver regeneration to elucidate the function of EpCAMs in the regenerating liver in vivo. Proliferating ductal cells were observed after severe hepatocyte loss in the zebrafish model. Analyses of the liver size as well as hepatocyte and BEC markers revealed successful conversion of LPCs to hepatocytes and BECs in epcam mutants. Notably, epcam mutants exhibited severe defects in intrahepatic duct maturation and bile acid secretion in regenerating hepatocytes, suggesting that epcam plays a critical role in intrahepatic duct reconstruction during LPC-driven liver regeneration. Our findings provide insights into human diseases involving non-parenchymal cells, such as primary biliary cholangitis, by highlighting the regulatory effect of epcam on intrahepatic duct reconstruction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping