Document Detail


The balance between Notch/Wnt signaling regulates progenitor cells' commitment during liver repair: Mystery solved?
MedLine Citation:
PMID:  22902547     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted.
Authors:
Mario Strazzabosco; Luca Fabris
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-15
Journal Detail:
Title:  Journal of hepatology     Volume:  -     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA; Department of Clinical Medicine, University of Milan-Bicocca, Milan, Italy.
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