Journal Article

A Key Role for E-cadherin in Intestinal Homeostasis and Paneth Cell Maturation

Trülzsch, Konrad, Müller-Höcker, Josef, Dahlhoff, Maik, Wolf, Eckhard, Horst, David, Hirschi, Benjamin, Schneider, Marlon R., Allgäuer, Michael, Gerhard, Markus, Steininger, Sylvia, Vogelmann, Roger, Kolligs, Frank T.

2010

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adherens junctions / Animals / Antibacterial agents / Antiinfectives and antibacterials / Apoptosis / Bacteria / Bacteroides fragilis / Cadherins - biosynthesis / Cadherins - physiology / CDH1 gene / Cdh1 Proteins / Cell adhesion & migration / Cell Biology/Cell Adhesion / Cell Cycle Proteins - genetics / Cell Cycle Proteins - metabolism / Cell Death / Cell differentiation / Cell lineage / Cell migration / Clearing / Colon / Colon - metabolism / Crohn Disease - metabolism / Crohn's disease / Deactivation / Developmental Biology/Cell Differentiation / Diarrhea / Differentiation (biology) / E-cadherin / Epithelial Cells - metabolism / Epithelium / Gastroenterology and Hepatology/Small Intestine / Gene Expression Regulation / Goblet cells / Goblet Cells - metabolism / Health aspects / Homeostasis / Homozygote / Immune system / Inactivation / Innate immunity / Intestine / Intestine, Small - metabolism / Maintenance / Maturation / Mice / Mice, Transgenic / Paneth cells / Paneth Cells - cytology / Pathogenesis / Rodents / Shedding / Small intestine / Villus