In GERD patients, mucosal repair associated genes are upregulated in non‐inflamed oesophageal epithelium

Abstract

Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6–12% and SAP ≥ 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P-value < 1E– 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell–cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function.

Bile Salts at Low pH Cause Dilation of Intercellular Spaces in In Vitro Stratified Primary Esophageal Cells, Possibly by Modulating Wnt Signaling

“…18 Even before the inflammation sets in, the epithelium actively battles the luminal assault by initiating epithelial restitution, a process in which anti-apoptotic, anti-oxidant, and cell migration promoting genes are activated to restore the epithelial integrity and barrier function. 19 Formation of DIS can arguably be viewed as a histological feature of a pro-migratory epithelium, where intercellular junctions are deregulated to facilitate the process of epithelial restitution.…”

Heat shock protein 27: Induction by gastroduodenal reflux in vivo and augmentation of human esophageal mucosal cell growth in vitro

“…5 Likewise, acid exposure of esophageal mucosa appears to upregulate several antiapoptotic and antioxidantassociated genes. 6 Our current understanding of the growth response in esophageal mucosa is minimal, and identification of new potential mediators of this response is critical.…”