PMID- 38224664 OWN - NLM STAT- MEDLINE DCOM- 20240202 LR - 20240206 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 696 DP - 2024 Feb 12 TI - Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model. PG - 149512 LID - S0006-291X(24)00047-0 [pii] LID - 10.1016/j.bbrc.2024.149512 [doi] AB - 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. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Lee, Siyeo AU - Lee S AD - Department of Pathology, Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, 54538, Republic of Korea; Department of Biomedical Science, Graduate School Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea. FAU - Memon, Azra AU - Memon A AD - Department of Pathology, Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, 54538, Republic of Korea. FAU - Chae, Soo-Cheon AU - Chae SC AD - Department of Pathology, Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, 54538, Republic of Korea. FAU - Shin, Donghun AU - Shin D AD - Department of Developmental Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA. FAU - Choi, Tae-Young AU - Choi TY AD - Department of Pathology, Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, 54538, Republic of Korea; Department of Biomedical Science, Graduate School Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea. Electronic address: choity76@wku.ac.kr. LA - eng PT - Journal Article DEP - 20240110 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Epithelial Cell Adhesion Molecule) SB - IM MH - Animals MH - Humans MH - *Zebrafish MH - Epithelial Cell Adhesion Molecule/genetics/metabolism MH - Liver/metabolism MH - Bile Ducts, Intrahepatic/metabolism MH - Hepatocytes/metabolism MH - Epithelial Cells/metabolism MH - *Cholangitis/pathology MH - Liver Regeneration OTO - NOTNLM OT - Epcam OT - Intrahepatic duct OT - Liver progenitor cells (LPCs) OT - Liver regeneration OT - Primary biliary cholangitis (PBC) OT - Zebrafish COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/16 00:42 MHDA- 2024/02/02 06:43 CRDT- 2024/01/15 18:02 PHST- 2023/11/13 00:00 [received] PHST- 2023/12/29 00:00 [revised] PHST- 2024/01/09 00:00 [accepted] PHST- 2024/02/02 06:43 [medline] PHST- 2024/01/16 00:42 [pubmed] PHST- 2024/01/15 18:02 [entrez] AID - S0006-291X(24)00047-0 [pii] AID - 10.1016/j.bbrc.2024.149512 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2024 Feb 12;696:149512. doi: 10.1016/j.bbrc.2024.149512. Epub 2024 Jan 10.