Document Detail


A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation.
MedLine Citation:
PMID:  21179475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: E-cadherin is a major component of adherens junctions. Impaired expression of E-cadherin in the small intestine and colon has been linked to a disturbed intestinal homeostasis and barrier function. Down-regulation of E-cadherin is associated with the pathogenesis of infections with enteropathogenic bacteria and Crohn's disease.
METHODS AND FINDINGS: To genetically clarify the function of E-cadherin in intestinal homeostasis and maintenance of the epithelial defense line, the Cdh1 gene was conditionally inactivated in the mouse intestinal epithelium. Inactivation of the Cdh1 gene in the small intestine and colon resulted in bloody diarrhea associated with enhanced apoptosis and cell shedding, causing life-threatening disease within 6 days. Loss of E-cadherin led cells migrate faster along the crypt-villus axis and perturbed cellular differentiation. Maturation and positioning of goblet cells and Paneth cells, the main cell lineage of the intestinal innate immune system, was severely disturbed. The expression of anti-bacterial cryptidins was reduced and mice showed a deficiency in clearing enteropathogenic bacteria from the intestinal lumen.
CONCLUSION: These results highlight the central function of E-cadherin in the maintenance of two components of the intestinal epithelial defense: E-cadherin is required for the proper function of the intestinal epithelial lining by providing mechanical integrity and is a prerequisite for the proper maturation of Paneth and goblet cells.
Authors:
Marlon R Schneider; Maik Dahlhoff; David Horst; Benjamin Hirschi; Konrad Trülzsch; Josef Müller-Höcker; Roger Vogelmann; Michael Allgäuer; Markus Gerhard; Sylvia Steininger; Eckhard Wolf; Frank T Kolligs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-14
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-12-23     Completed Date:  2011-07-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e14325     Citation Subset:  IM    
Affiliation:
Institute of Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, University of Munich, Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / biosynthesis,  physiology*
Cell Cycle Proteins / genetics*,  metabolism
Cell Death
Colon / metabolism
Crohn Disease / metabolism
Epithelial Cells / metabolism
Gene Expression Regulation*
Goblet Cells / metabolism
Homeostasis
Homozygote
Intestine, Small / metabolism
Mice
Mice, Transgenic
Paneth Cells / cytology*
Chemical
Reg. No./Substance:
0/Cadherins; 0/Cell Cycle Proteins; 0/Fzr1 protein, mouse
Comments/Corrections

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