Assessment of desmosomal components (desmoglein 1-3, plakoglobin) in cardia mucosa in relation to gastroesophageal reflux disease and Helicobacter pylori infection.

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.

Gastro-oesophageal reflux disease is associated with up-regulation of desmosomal components in oesophageal mucosa.

AIMS: 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. METHODS AND 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.

Gastroesophageal reflux disease does not lead to changes in the secretory leukocyte protease inhibitor expression in esophageal mucosa.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) serves as a 'defense shield' against serine proteases in inflammation. Gastroesophageal reflux disease (GERD) is associated with chronic inflammation and histomorphological alterations of the gastroesophageal junction and esophageal mucosa. Here, it was investigated whether the presence of GERD was associated with changes of mucosal SLPI expression. METHODS: Ninety-five patients with GERD-related symptoms and 27 patients lacking those symptoms were included. Endoscopic and histological evaluation was done according to the Los Angeles and updated Sydney classifications. Multiple biopsies were taken from gastric and esophageal mucosa of each patient for histology, immunohistochemistry (IHC), and molecular analyses. SLPI expression was analyzed by quantitative reverse transcriptase-PCR, enzyme-linked immunoassay, and IHC, and the data were statistically analyzed with respect to endoscopic and clinical parameters. RESULTS: Forty-four patients had nonerosive and 51 erosive reflux diseases, respectively. Histology revealed higher chronic inflammation (P=0.04) and significant alterations of the intercellular spaces, basal cell hyperplasia, and length of papilla (P<0.05) in patients with GERD. Mucosal SLPI levels were comparable among antrum, cardia, and esophagus ranging from 95 to 165 pg/mug protein and were not affected by the presence of GERD, whereas esophageal SLPI-transcript levels were three-fold induced in patients with GERD (P=0.002). IHC identified epithelial cells as major cellular source of mucosal SLPI expression in normal cardiac and esophageal mucosa, whereas infiltrating immune cells contributed to the SLPI expression in chronically inflamed tissue. CONCLUSION: GERD, a chemically induced inflammation, does not affect mucosal SLPI expression in gastroesophageal mucosa.