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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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 >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.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/j.1582-4934.2008.00626.x</identifier><identifier>PMID: 19413890</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>Journal of cellular and molecular medicine, 2009-05, Vol.13 (5), p.936-947</ispartof><rights>2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd</rights><rights>Copyright Blackwell Publishing Ltd. May 2009</rights><rights>2009. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). 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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%. 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.</description><subject>Acids</subject><subject>Adult</subject><subject>Aged</subject><subject>Antacids</subject><subject>Apoptosis</subject><subject>Biopsy</subject><subject>Cells</subject><subject>Cytoskeleton</subject><subject>Disease</subject><subject>DNA microarrays</subject><subject>Drug therapy</subject><subject>Endoscopy</subject><subject>Epithelial cells</subject><subject>epithelial restitution</subject><subject>Epithelium</subject><subject>Esophagus</subject><subject>Esophagus - metabolism</subject><subject>Female</subject><subject>Gastroesophageal reflux</subject><subject>Gastroesophageal Reflux - metabolism</subject><subject>gastroesophageal reflux disease</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genome-Wide Association Study</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Male</subject><subject>microarray expression profiling</subject><subject>Middle Aged</subject><subject>Mucous Membrane - metabolism</subject><subject>oesophageal epithelial defense</subject><subject>oesophagus</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oxidants</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Questionnaires</subject><subject>Software packages</subject><subject>Up-Regulation</subject><subject>Variance analysis</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkdtu1DAQhiMEoqXwCsgCiSs2-BTHuQAJbUspaoWE4NqaTSa7jrJ2aie0veMReEaeBKe7KgcJCd94NPPNPzP6s4wwmrP0XnU5KzRfyErInFOqc0oVV_n1vezwrnB_HzMt9EH2KMaOUqGYqB5mB6ySTOiKHmbdmSOnJ5-OyQCjRTfGl2Q71T5CTwIOYAOBGH1tYcSGrNFhJBCQTEPA9dTfZq0jzrsf375b1_awTRmP0Q8bWGNSwcGOG-zttH2cPWihj_hk_x9lX96dfF6-X5x_PD1bvj1f1AUv1UI1suS6XfEi7QtYUahFWTS0aGmra8ZrxQGKggOCSAmxAkEbJSvGm0atFIij7M1Od5hWaZs6XRWgN0OwWwg3xoM1f1ac3Zi1_2qE5kLSKgm82AsEfzlhHM3Wxhr7Hhz6KRpVSlpwWSTw-V9g56fg0nFG0FIqzbQUiXr2L4qzMiFSzzP1DqqDjzFge7cvo2b23HRmttPM1prZc3PrublOrU9_v_dX497kBLzeAVe2x5v_FjYflhcXKRI_AUZvvMs</recordid><startdate>200905</startdate><enddate>200905</enddate><creator>De Vries, D. 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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. 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R.</au><au>Ter Linde, J. J. M.</au><au>Van Herwaarden, M. A.</au><au>Schwartz, M. P.</au><au>Shephard, P.</au><au>Geng, M. M.</au><au>Smout, A. J. P. M.</au><au>Samsom, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In GERD patients, mucosal repair associated genes are upregulated in non‐inflamed oesophageal epithelium</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2009-05</date><risdate>2009</risdate><volume>13</volume><issue>5</issue><spage>936</spage><epage>947</epage><pages>936-947</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19413890</pmid><doi>10.1111/j.1582-4934.2008.00626.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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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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