Article Text

Download PDFPDF
Original article
Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease


Background Epithelial barrier defects are well known in coeliac disease, but the mechanisms are only poorly defined. It is unclear, whether barrier disturbance reflects upregulated epithelial transcytosis or paracellular leakage.

Objective To characterise the molecular structure and function of the epithelial tight junction (TJ) and mechanisms of its dysregulation.

Methods Molecular analysis of proteins involved in TJ assembly and their regulation was performed by western blotting and confocal microscopy correlated to electrophysiology.

Results A complex alteration of the composition of epithelial TJ proteins (with more pore-forming claudins like claudin-2 and a reduction in tightening claudins like claudin-3, -5 and -7) was found for protein expression and subcellular localisation, responsible for an increase in paracellular biotin-NHS uptake. In contrast, epithelial apoptosis was only moderately elevated (accounting for a minor portion of barrier defects) and epithelial gross lesions—for example, at cell extrusion zones, were absent. This TJ alteration was linked to an altered localisation/expression of proteins regulating TJ assembly, the polarity complex protein Par-3 and the serine-/threonine phosphatase PP-1.

Conclusions Changes in cell polarity proteins Par-3 and PP-1 are associated with altered expression and assembly of TJ proteins claudin-2, -3, -5 and -7 and ZO-1, causing paracellular leakage in active coeliac disease.

  • Celiac disease
  • epithelial barrier
  • Par-3
  • tight junction
  • apoptosis
  • gastrointestinal lymphoma
  • gamma delta t cells
  • lamina proprial lymphocytes
  • coeliac disease
  • enteropathy
  • endoscopy
  • new imaging technologies
  • confocal laser endomicroscopy
  • chromoendoscopy
  • endoscopic retrograde pancreatography
  • endoscopic ultrasonography
  • endoscopic polypectomy
  • adenoma
  • endoscopic procedures
  • gut immunology
  • epithelial permeability
  • epithelial transport
  • Crohn's disease
  • inflammatory bowel disease
  • mucosal immunology
  • HIV-related gastrointestinal disease
  • Helicobacter pylori
  • acid-related diseases
  • non-ulcer dyspepsia
  • genetic polymorphisms
  • gastric neoplasia
  • inflammation
  • IBD
  • 5-aminosalicylic acid (5-ASA)
  • inflammatory mechanisms
  • radiation enteritis
  • apoptosis
View Full Text

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.