PMID- 24812054
OWN - NLM
STAT- MEDLINE
DCOM- 20140829
LR  - 20171116
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 307
IP  - 1
DP  - 2014 Jul 1
TI  - Epiregulin promotes the emergence and proliferation of adult liver progenitor 
      cells.
PG  - G50-7
LID - 10.1152/ajpgi.00434.2013 [doi]
AB  - We have previously reported that epiregulin is a growth factor that seems to act 
      on liver progenitor cells (LPCs) during liver regeneration. However, the 
      relationship between epiregulin and LPCs has remained unclear. The aim of the 
      present study was to clarify the role of epiregulin during liver regeneration. 
      The serum levels of epiregulin in patients with acute liver failure were 
      examined. A liver injury model was developed using mice fed a diet containing 
      0.1% 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) to induce LPCs. We then 
      evaluated the expression of epiregulin and LPCs in these mice. The proliferation 
      of epithelial cell adhesion molecule + LPCs cultured with epiregulin was examined 
      in vitro, and finally epiregulin was overexpressed in mouse liver. In patients 
      with acute liver failure, serum epiregulin levels were elevated significantly. In 
      DDC mice, LPCs emerged around the portal area. Epiregulin was also detected 
      around the portal area during the course of DDC-induced liver injury and was 
      partially coexpressed with Thy1. Serum epiregulin levels in DDC mice were also 
      significantly elevated. Recombinant epiregulin augmented the proliferative 
      capacity of the LPCs in a dose-dependent manner. In mice showing overexpression 
      of epiregulin, the expression of PCNA on hepatocytes was increased significantly. 
      Finally, LPCs emerged around the portal area after epiregulin gene delivery. We 
      concluded that epiregulin promotes the proliferation of LPCs and DNA synthesis by 
      hepatocytes and is upregulated in the serum of patients with liver injury. 
      Furthermore, induction of epiregulin leads to the appearance of LPCs. Epiregulin 
      would be a useful biomarker of liver regeneration.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Tomita, Kyoko
AU  - Tomita K
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan; CREST, Yamagata University Faculty of Medicine, Yamagata, Japan 
      to.kyoko@med.id.yamagata-u.ac.jp.
FAU - Haga, Hiroaki
AU  - Haga H
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan;
FAU - Mizuno, Kei
AU  - Mizuno K
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan; CREST, Yamagata University Faculty of Medicine, Yamagata, Japan.
FAU - Katsumi, Tomohiro
AU  - Katsumi T
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan;
FAU - Sato, Chikako
AU  - Sato C
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan; CREST, Yamagata University Faculty of Medicine, Yamagata, Japan.
FAU - Okumoto, Kazuo
AU  - Okumoto K
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan;
FAU - Nishise, Yuko
AU  - Nishise Y
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan;
FAU - Watanabe, Hisayoshi
AU  - Watanabe H
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan; CREST, Yamagata University Faculty of Medicine, Yamagata, Japan.
FAU - Saito, Takafumi
AU  - Saito T
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan;
FAU - Ueno, Yoshiyuki
AU  - Ueno Y
AD  - Department of Gastroenterology, Yamagata University Faculty of Medicine, 
      Yamagata, Japan; CREST, Yamagata University Faculty of Medicine, Yamagata, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140508
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (EREG protein, human)
RN  - 0 (Epiregulin)
RN  - 0 (Epithelial Cell Adhesion Molecule)
RN  - 0 (Ereg protein, mouse)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thy-1 Antigens)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Adult
MH  - Adult Stem Cells/drug effects/*metabolism/pathology
MH  - Animals
MH  - Antigens, Neoplasm/metabolism
MH  - Cell Adhesion Molecules/metabolism
MH  - Cell Line
MH  - *Cell Proliferation/drug effects
MH  - DNA Replication
MH  - Dose-Response Relationship, Drug
MH  - Epidermal Growth Factor/blood/genetics/*metabolism/pharmacology
MH  - Epiregulin
MH  - Epithelial Cell Adhesion Molecule
MH  - Female
MH  - Humans
MH  - Liver/drug effects/*metabolism/pathology
MH  - Liver Diseases/blood/genetics/*metabolism/pathology
MH  - *Liver Regeneration/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Recombinant Proteins/pharmacology
MH  - Thy-1 Antigens/metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Thy1
OT  - epiregulin
OT  - epithelial cell adhesion molecule
OT  - liver injury
OT  - liver regeneration
OT  - progenitor cells
EDAT- 2014/05/09 06:00
MHDA- 2014/08/30 06:00
CRDT- 2014/05/10 06:00
PHST- 2014/05/10 06:00 [entrez]
PHST- 2014/05/09 06:00 [pubmed]
PHST- 2014/08/30 06:00 [medline]
AID - ajpgi.00434.2013 [pii]
AID - 10.1152/ajpgi.00434.2013 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2014 Jul 1;307(1):G50-7. doi: 
      10.1152/ajpgi.00434.2013. Epub 2014 May 8.