title: Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.
abstract: BACKGROUND
  Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms.
  
  
  METHODS
  Junctional proteins were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34) comprising both alternating (IBS-A) and diarrhea predominant (IBS-D) subtypes, and controls (n = 12). IBS symptom duration, abdominal pain severity and stool frequency were assessed for IBS patients. Protein expression was determined by immunofluorescence.
  
  
  RESULTS
  E-cadherin and ZO-1 protein expression was significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface epithelium of the IBS group comprising both IBS-A and IBS-D subtypes. CLD-1 expression was not significantly altered compared with controls. On subtype analysis, ZO-1 expression was significantly reduced in both IBS-A and IBS-D compared with controls, whereas E-cadherin was reduced only in IBS-A. Lower E-cadherin expression was associated with longer symptoms duration specifically in IBS-A patients (rs = -0.76, p = 0.004). Reduced E-cadherin associated with abdominal pain severity in the overall IBS group (rs = -0.36, p = 0.041), but this association was unrelated to IBS subtype.
  
  
  CONCLUSIONS
  E-cadherin protein expression in the cecum was significantly lower in IBS-A compared with controls and associated with longstanding symptoms. E-cadherin was further associated with abdominal pain severity in the IBS group overall, but unrelated to IBS subtype. Altered E-cadherin expression may provide novel insights into mechanisms underlying intestinal barrier dysfunction in IBS.
authors.affiliation: Department of Clinical Medicine, Trinity Centre for Health Sciences, Adelaide & Meath Hospital, Dublin, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Wilcz-Villega
authors.forename: S
authors.initials: S
authors.lastname: McClean
authors.forename: M
authors.initials: M
authors.lastname: O'Sullivan
mesh_terms: D015746:Abdominal Pain / Q000378:metabolism; D000328:Adult; D015820:Cadherins / Q000378:metabolism*; D002432:Cecum / Q000378:metabolism*; D062445:Claudin-1 / Q000378:metabolism; D003967:Diarrhea / Q000378:metabolism; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: E-cadherin; ZO-1; adherens junction proteins; intestinal permeability; irritable bowel syndrome (IBS); tight junction proteins