PMID- 29690953
OWN - NLM
STAT- MEDLINE
DCOM- 20190529
LR  - 20230928
IS  - 1052-2166 (Print)
IS  - 1555-3884 (Electronic)
IS  - 1052-2166 (Linking)
VI  - 18
IP  - 3
DP  - 2018 Aug 22
TI  - Stat3 Regulates Liver Progenitor Cell-Driven Liver Regeneration in Zebrafish.
PG  - 157-170
LID - 10.3727/105221618X15242506133273 [doi]
AB  - After liver injury, regeneration manifests as either (1) hepatocytes 
      proliferating to restore the lost hepatocyte mass or (2) if hepatocyte 
      proliferation is compromised, biliary epithelial cells (BECs) dedifferentiating 
      into liver progenitor cells (LPCs), which subsequently differentiate into 
      hepatocytes. Following pharmacogenetic ablation of hepatocytes in 
      Tg(fabp10a:CFP-NTR) zebrafish, resulting in severe liver injury, signal 
      transducer and activator of transcription 3 (Stat3) and its target gene and 
      negative regulator, socs3a, were upregulated in regenerating livers. Using either 
      Stat3 inhibitors, JSI-124 and S3I-201, or stat3 zebrafish mutants, we 
      investigated the role of Stat3 in LPC-driven liver regeneration. Although Stat3 
      suppression reduced the size of regenerating livers, BEC dedifferentiation into 
      LPCs was unaffected. However, regenerating livers displayed a delay in 
      LPC-to-hepatocyte differentiation and a significant reduction in the number of 
      BECs. While no difference in cell death was detected, Stat3 inhibition 
      significantly reduced LPC proliferation. Notably, stat3 mutants phenocopied the 
      effects of Stat3 chemical inhibitors, although the mutant phenotype was 
      incompletely penetrant. Intriguingly, a subset of socs3a mutants also displayed a 
      lower number of BECs in regenerating livers. We conclude that the Stat3/Socs3a 
      pathway is necessary for the proper timing of LPC-to-hepatocyte differentiation 
      and establishing the proper number of BECs during LPC-driven liver regeneration.
FAU - Khaliq, Mehwish
AU  - Khaliq M
AD  - Department of Developmental Biology, McGowan Institute for Regenerative Medicine, 
      Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
FAU - Ko, Sungjin
AU  - Ko S
AD  - Department of Developmental Biology, McGowan Institute for Regenerative Medicine, 
      Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
FAU - Liu, Yinzi
AU  - Liu Y
AD  - Department of Developmental Biology, Washington University School of Medicine, 
      St. Louis, MO, USA.
FAU - Wang, Hualin
AU  - Wang H
AD  - China Zebrafish Resource Center, State Key Laboratory of Freshwater Ecology and 
      Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 
      P.R. China.
FAU - Sun, Yonghua
AU  - Sun Y
AD  - China Zebrafish Resource Center, State Key Laboratory of Freshwater Ecology and 
      Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 
      P.R. China.
FAU - Solnica-Krezel, Lila
AU  - Solnica-Krezel L
AD  - Department of Developmental Biology, Washington University School of Medicine, 
      St. Louis, MO, USA.
FAU - Shin, Donghun
AU  - Shin D
AD  - Department of Developmental Biology, McGowan Institute for Regenerative Medicine, 
      Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
LA  - eng
GR  - F31 DK105714/DK/NIDDK NIH HHS/United States
GR  - P01 HD084387/HD/NICHD NIH HHS/United States
GR  - R01 DK101426/DK/NIDDK NIH HHS/United States
GR  - R35 GM118179/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180424
PL  - United States
TA  - Gene Expr
JT  - Gene expression
JID - 9200651
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (socs3a protein, zebrafish)
RN  - 0 (stat3 protein, zebrafish)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Hepatocytes/cytology/*metabolism
MH  - *Liver Regeneration
MH  - STAT3 Transcription Factor/antagonists & inhibitors/genetics/*metabolism
MH  - Stem Cells/cytology/metabolism
MH  - Suppressor of Cytokine Signaling 3 Protein/genetics/metabolism
MH  - Zebrafish
MH  - Zebrafish Proteins/antagonists & inhibitors/genetics/*metabolism
PMC - PMC6190120
COIS- The authors declare no conflicts of interests.
EDAT- 2018/04/25 06:00
MHDA- 2019/05/30 06:00
PMCR- 2018/08/22
CRDT- 2018/04/26 06:00
PHST- 2018/04/25 06:00 [pubmed]
PHST- 2019/05/30 06:00 [medline]
PHST- 2018/04/26 06:00 [entrez]
PHST- 2018/08/22 00:00 [pmc-release]
AID - GE386 [pii]
AID - 10.3727/105221618X15242506133273 [doi]
PST - ppublish
SO  - Gene Expr. 2018 Aug 22;18(3):157-170. doi: 10.3727/105221618X15242506133273. Epub 
      2018 Apr 24.