PMID- 32087972
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
DP  - 2020 Feb 19
TI  - EpCAM inhibits differentiation of human liver progenitor cells into hepatocytes 
      in vitro by activating Notch1 signaling.
LID - S0006-291X(20)30309-0 [pii]
LID - 10.1016/j.bbrc.2020.02.041 [doi]
AB  - In both normal turnover of the hepatic tissue and acute hepatic injury, the liver 
      predominantly activates terminally differentiated hepatocytes to proliferate and 
      repair. However, in chronic and severe chronic injury, this capacity fails, and 
      liver progenitor cells (LPCs) can give rise to hepatocytes to restore both 
      hepatic architecture and liver metabolic function. Although the promotion of 
      LPC-to-hepatocyte differentiation to acquire a considerable number of functional 
      hepatocytes could serve as a potentially new therapeutic option for patients with 
      end-stage liver disease, its development first requires the identification of the 
      molecular mechanisms driving this process. Here, we found that the epithelial 
      cell adhesion molecule (EpCAM), a progenitor cell marker, regulates the 
      differentiation of LPCs into hepatocytes through Notch1 signaling pathway. 
      Western blotting (WB) revealed a consistent expression pattern of EpCAM and 
      Notch1 during LPC-to-hepatocyte differentiation in vitro. Additionally, 
      overexpression of EpCAM blocked LPC-to-hepatocyte differentiation, which was in 
      consistent with the repressive role of Notch signaling during hepatic 
      differentiation. WB and immunofluorescence data also showed that the upregulation 
      of EpCAM expression increased the generation of Notch intracellular domain 
      (N(1)ICD), indicating the promotion of Notch1 activity. Our results established 
      the EpCAM-Notch1 signaling axis as an inhibitory mechanism preventing 
      LPC-to-hepatocyte differentiation in vitro.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Tang, Dan
AU  - Tang D
AD  - Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai, China.
FAU - Chen, Yi
AU  - Chen Y
AD  - Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai, China.
FAU - Fu, Gong-Bo
AU  - Fu GB
AD  - International Cooperation Laboratory on Signal Transduction, Eastern 
      Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 
      China.
FAU - Yuan, Tian-Jie
AU  - Yuan TJ
AD  - Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai, China.
FAU - Huang, Wei-Jian
AU  - Huang WJ
AD  - International Cooperation Laboratory on Signal Transduction, Eastern 
      Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 
      China.
FAU - Wang, Zhen-Yu
AU  - Wang ZY
AD  - Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Li, Wei-Jian
AU  - Li WJ
AD  - Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Jiao, Ying-Fu
AU  - Jiao YF
AD  - Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai, China. Electronic address: 
      yingfujiao@yeah.net.
FAU - Yu, Wei-Feng
AU  - Yu WF
AD  - Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai, China. Electronic address: 
      ywf808@yeah.net.
FAU - Yan, He-Xin
AU  - Yan HX
AD  - Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai, China; Department of 
      Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, China. Electronic address: hexinyw@163.com.
LA  - eng
PT  - Journal Article
DEP - 20200219
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
SB  - IM
OTO - NOTNLM
OT  - EpCAM
OT  - HepaRG
OT  - LPC-To-hepatocyte differentiation
OT  - Notch1
COIS- Declaration of competing interest The authors declared no conflicts of interests.
EDAT- 2020/02/24 06:00
MHDA- 2020/02/24 06:00
CRDT- 2020/02/24 06:00
PHST- 2020/01/14 00:00 [received]
PHST- 2020/02/08 00:00 [accepted]
PHST- 2020/02/24 06:00 [entrez]
PHST- 2020/02/24 06:00 [pubmed]
PHST- 2020/02/24 06:00 [medline]
AID - S0006-291X(20)30309-0 [pii]
AID - 10.1016/j.bbrc.2020.02.041 [doi]
PST - aheadofprint
SO  - Biochem Biophys Res Commun. 2020 Feb 19:S0006-291X(20)30309-0. doi: 
      10.1016/j.bbrc.2020.02.041.