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Publication : A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation.

First Author  Schneider MR Year  2010
Journal  PLoS One Volume  5
Issue  12 Pages  e14325
PubMed ID  21179475 Mgi Jnum  J:168992
Mgi Id  MGI:4939522 Doi  10.1371/journal.pone.0014325
Citation  Schneider MR, et al. (2010) A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation. PLoS One 5(12):e14325
abstractText  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.
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