title: Role of tight junction proteins in gastroesophageal reflux disease.
abstract: BACKGROUND
  Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function that is regulated by cell-cell contacts. The aim of the study was to investigate the expression pattern of selected components involved in the formation of tight junctions in relation to GERD.
  
  
  METHODS
  Eighty-four patients with GERD-related symptoms with endoscopic signs (erosive: n = 47) or without them (non-erosive: n = 37) as well as 26 patients lacking GERD-specific symptoms as controls were included. Endoscopic and histological characterization of esophagitis was performed according to the Los Angeles and adapted Ismeil-Beigi criteria, respectively. Mucosal biopsies from distal esophagus were taken for analysis by histopathology, immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (RT-PCR) of five genes encoding tight junction components [Occludin, Claudin-1, -2, Zona occludens (ZO-1, -2)].
  
  
  RESULTS
  Histopathology confirmed GERD-specific alterations as dilated intercellular spaces in the esophageal mucosa of patients with GERD compared to controls (P < 0.05). Claudin-1 and -2 were 2- to 6-fold upregulation on transcript (P < 0.01) and in part on protein level (P < 0.015) in GERD, while subgroup analysis of revealed this upregulation for ERD only. In both erosive and non-erosive reflux disease, expression levels of Occludin and ZO-1,-2 were not significantly affected. Notably, the induced expression of both claudins did not correlate with histopathological parameters (basal cell hyperplasia, dilated intercellular spaces) in patients with GERD.
  
  
  CONCLUSIONS
  Taken together, the missing correlation between the expression of tight junction-related components and histomorphological GERD-specific alterations does not support a major role of the five proteins studied in the pathogenesis of GERD.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Magdeburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mönkemüller
authors.forename: Thomas
authors.initials: T
authors.lastname: Wex
authors.forename: Doerthe
authors.initials: D
authors.lastname: Kuester
authors.forename: Lucia C
authors.initials: LC
authors.lastname: Fry
authors.forename: Arne
authors.initials: A
authors.lastname: Kandulski
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000328:Adult; D000368:Aged; D004941:Esophagitis / Q000473:pathology / Q000503:physiopathology; D004945:Esophagoscopy; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology / Q000503:physiopathology*; D005773:Gastroscopy; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D062725:Tight Junction Proteins / Q000235:genetics / Q000502:physiology*; D055815:Young Adult
chemical_list: D062725:Tight Junction Proteins