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.