title: Intestinal E-cadherin Deficiency Aggravates Dextran Sodium Sulfate-Induced Colitis.
abstract: BACKGROUND
  E-cadherin is a cell adhesion protein with crucial roles in development, tissue homeostasis, and disease. Loss of E-cadherin in the adult intestinal epithelium disrupts tissue architecture and is associated with impaired localization and function of goblet and Paneth cells, reduced expression of antibacterial factors, and deficiency in clearing enteropathogenic bacteria. Several studies have suggested a role of E-cadherin in human inflammatory bowel disease.
  
  
  OBJECTIVE
  To investigate the role of E-cadherin deficiency in the pathogenesis of inflammatory bowel disease in a mouse model of experimentally induced colitis.
  
  
  METHODS
  To induce E-cadherin deficiency, Villin-Cre-ER (T2) ;Cdh1 (fl/fl) mice received intraperitoneal injections of tamoxifen at days 1, 2, 5, and 8. Experimental colitis was induced by oral administration of dextran sodium sulfate (DSS, 3.5 % in the drinking water) for 3 days, starting at the third day after the first tamoxifen injection.
  
  
  RESULTS
  E-cadherin deficiency in the adult mouse intestinal epithelium aggravates the clinical and histological features of DSS-induced colitis. Upon DSS treatment, mice deficient in E-cadherin lost more weight, were more severely dehydrated, and showed more frequently blood in the feces. Histologically, intestinal E-cadherin deficiency was associated with exacerbated acute and chronic inflammation and increased regenerative epithelial changes. Finally, the changes in the epithelium were distributed more diffusely in E-cadherin-deficient mice, while the mucosal damage was more focally localized in control animals.
  
  
  CONCLUSIONS
  Our findings suggest that E-cadherin may play an important role in the pathogenesis of ulcerative colitis, one of the major clinical forms of inflammatory bowel disease.
authors: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Feodor-Lynen-Str. 25, 81377, Munich, Germany.
authors: Jessica I
authors: JI
authors: Grill
authors: Jens
authors: J
authors: Neumann
authors: Felix
authors: F
authors: Hiltwein
authors: Frank T
authors: FT
authors: Kolligs
authors: Marlon R
authors: MR
authors: Schneider
mesh_terms: D000818:Animals; D015820:Cadherins / Q000172:deficiency*; D003092:Colitis / Q000209:etiology* / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D015820:Cadherins; D016264:Dextran Sulfate
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