title: Gastro-oesophageal reflux disease is associated with up-regulation of desmosomal components in oesophageal mucosa.
abstract: OBJECTIVE
  Gastro-oesophageal reflux disease (GERD) is associated with impaired epithelial barrier function. This study was aimed at investigating the role of desmosomal proteins in relation to GERD.
  
  
  RESULTS
  Ninety-five patients with GERD-related symptoms (erosive, n = 51; non-erosive, n = 44) and 27 patients lacking those symptoms were included. Endoscopic and histological characterization of oesophagitis was performed according to the Los Angeles and Ismeil-Beigi criteria, respectively. Multiple biopsies were taken from the oesophageal mucosa of each patient. Gene expression analysis of plakoglobin, desmoglein-1, desmoglein-2 and desmoglein-3 was performed by quantitative real time (RT)-polymerase chain reaction and immunohistochemistry in the oesophageal mucosa. Routine histology revealed specific GERD-related alterations, such as dilatation of intercellular spaces (DIS), basal cell hyperplasia (BCH), and elongation of the papillae, in the oesophageal mucosa of patients with GERD, as compared with controls (all parameters: P < 0.05). All four genes and corresponding proteins were found to be up-regulated by between 1.7 and 8.1-fold (transcript level, P < 0.05; protein level, P < 0.05). Induced gene expression levels of plakoglobin, desmoglein-1 and desmoglein-2 correlated significantly with DIS and BCH.
  
  
  CONCLUSIONS
  Taken together, the uniform up-regulation of desmosomal genes/proteins in the oesophageal mucosa of patients with GERD supports the concept of architectural and molecular changes in the desmosomal compartment in the pathogenesis of GERD.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany. thomas.wex@med.ovgu.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Wex
authors.forename: Klaus
authors.initials: K
authors.lastname: Mönkemüller
authors.forename: Antje
authors.initials: A
authors.lastname: Stahr
authors.forename: Doerthe
authors.initials: D
authors.lastname: Kuester
authors.forename: Lucia C
authors.initials: LC
authors.lastname: Fry
authors.forename: Simone
authors.initials: S
authors.lastname: Völkel
authors.forename: Arne
authors.initials: A
authors.lastname: Kandulski
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D051182:Desmogleins / Q000235:genetics* / Q000378:metabolism; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016099:Endoscopy, Gastrointestinal / Q000379:methods; D004941:Esophagitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D011446:Prospective Studies; D015854:Up-Regulation; D055815:Young Adult; D051185:gamma Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051182:Desmogleins; D051185:gamma Catenin