title: Assessment of desmosomal components (desmoglein 1-3, plakoglobin) in cardia mucosa in relation to gastroesophageal reflux disease and Helicobacter pylori infection.
abstract: Gastroesophageal reflux disease is associated with impaired epithelial barrier function and abnormal expression of proteins forming cell-cell contacts by tight junctions and desmosomes in distal esophageal squamous mucosa. Although gastroesophageal reflux disease and Helicobacter pylori are both associated with chronic inflammation of the adjacent cardia mucosa, it is not known whether these lead to derangements of the desmosomal complexes. Here, we assessed the expression of 4 proteins (plakoglobin and desmoglein 1, 2, and 3) forming epithelial desmosomal complexes by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in biopsies from 67 patients with gastroesophageal reflux disease and 23 gastroesophageal reflux disease-negative controls. Plakoglobin and desmoglein 2 were ubiquitously expressed in all samples, whereas desmoglein 1 and 3 were not expressed in cardia mucosa. Gastroesophageal reflux disease was specifically associated with elevated transcript levels of desmoglein 2 and plakoglobin. These were significantly increased from 2.0- to 2.7-fold in patients with gastroesophageal reflux disease compared with controls (P < .01), and significantly increased immunohistochemical scores for both proteins were observed (P < .05) as well. The combined presence of gastroesophageal reflux disease and Helicobacter pylori infection had no additional effect on desmosomal gene expression. Taken together, the up-regulation of plakoglobin and desmoglein 2 in cardia mucosa of patients with gastroesophageal reflux disease supports the concept that the "transition zone" between distal esophagus and proximal stomach is affected by gastroesophageal reflux disease as well, and architectural and molecular changes in the desmosomal compartment contribute to the pathogenesis of gastroesophageal reflux disease in the cardia mucosa.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany. thomas.wex@med.ovgu.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Wex
authors.forename: Doerthe
authors.initials: D
authors.lastname: Kuester
authors.forename: Klaus
authors.initials: K
authors.lastname: Mönkemüller
authors.forename: Antje
authors.initials: A
authors.lastname: Stahr
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; D002299:Cardia / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051183:Desmoglein 1 / Q000032:analysis / Q000096:biosynthesis; D051301:Desmoglein 2 / Q000032:analysis / Q000096:biosynthesis; D051184:Desmoglein 3 / Q000032:analysis / Q000096:biosynthesis; D003896:Desmosomes / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000378:metabolism* / Q000382:microbiology*; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult; D051185:gamma Catenin / Q000032:analysis / Q000096:biosynthesis
chemical_list: D051183:Desmoglein 1; D051301:Desmoglein 2; D051184:Desmoglein 3; D051185:gamma Catenin