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

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...

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Veröffentlicht in:Journal of cellular and molecular medicine 2009-05, Vol.13 (5), p.936-947
Hauptverfasser: De Vries, D. R., Ter Linde, J. J. M., Van Herwaarden, M. A., Schwartz, M. P., Shephard, P., Geng, M. M., Smout, A. J. P. M., Samsom, M.
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container_issue 5
container_start_page 936
container_title Journal of cellular and molecular medicine
container_volume 13
creator De Vries, D. R.
Ter Linde, J. J. M.
Van Herwaarden, M. A.
Schwartz, M. P.
Shephard, P.
Geng, M. M.
Smout, A. J. P. M.
Samsom, M.
description 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.
doi_str_mv 10.1111/j.1582-4934.2008.00626.x
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R. ; Ter Linde, J. J. M. ; Van Herwaarden, M. A. ; Schwartz, M. P. ; Shephard, P. ; Geng, M. M. ; Smout, A. J. P. M. ; Samsom, M.</creator><creatorcontrib>De Vries, D. R. ; Ter Linde, J. J. M. ; Van Herwaarden, M. A. ; Schwartz, M. P. ; Shephard, P. ; Geng, M. M. ; Smout, A. J. P. M. ; Samsom, M.</creatorcontrib><description>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 &gt;1.4 (t‐test P‐value &lt; 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. 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R.</creatorcontrib><creatorcontrib>Ter Linde, J. J. M.</creatorcontrib><creatorcontrib>Van Herwaarden, M. A.</creatorcontrib><creatorcontrib>Schwartz, M. P.</creatorcontrib><creatorcontrib>Shephard, P.</creatorcontrib><creatorcontrib>Geng, M. M.</creatorcontrib><creatorcontrib>Smout, A. J. P. M.</creatorcontrib><creatorcontrib>Samsom, M.</creatorcontrib><title>In GERD patients, mucosal repair associated genes are upregulated in non‐inflamed oesophageal epithelium</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>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%. 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subjects Acids
Adult
Aged
Antacids
Apoptosis
Biopsy
Cells
Cytoskeleton
Disease
DNA microarrays
Drug therapy
Endoscopy
Epithelial cells
epithelial restitution
Epithelium
Esophagus
Esophagus - metabolism
Female
Gastroesophageal reflux
Gastroesophageal Reflux - metabolism
gastroesophageal reflux disease
Gene expression
Gene Expression Profiling
Gene regulation
Genes
Genome-Wide Association Study
Genotype & phenotype
Humans
Inflammation
Male
microarray expression profiling
Middle Aged
Mucous Membrane - metabolism
oesophageal epithelial defense
oesophagus
Oligonucleotide Array Sequence Analysis
Oxidants
Patients
Phenotypes
Questionnaires
Software packages
Up-Regulation
Variance analysis
title In GERD patients, mucosal repair associated genes are upregulated in non‐inflamed oesophageal epithelium
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