Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease
•GRß overexpression rendered Caco-2 cells steroid insensitive.•GRß was located in the nucleus and had an GRα independent transcriptional activity.•GRß regulated the expression of numerous involved in intact barrier function. The glucocorticoid receptor (GR) plays a crucial role in inflammatory respo...
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| Veröffentlicht in: | The Journal of steroid biochemistry and molecular biology 2016-01, Vol.155 (Pt A), p.76-84 |
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| creator | Nagy, Zsolt Acs, Bence Butz, Henriett Feldman, Karolina Marta, Alexa Szabo, Peter M. Baghy, Kornelia Pazmany, Tamas Racz, Karoly Liko, Istvan Patocs, Attila |
| description | •GRß overexpression rendered Caco-2 cells steroid insensitive.•GRß was located in the nucleus and had an GRα independent transcriptional activity.•GRß regulated the expression of numerous involved in intact barrier function.
The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies. |
| doi_str_mv | 10.1016/j.jsbmb.2015.10.006 |
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The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies.</description><identifier>ISSN: 0960-0760</identifier><identifier>EISSN: 1879-1220</identifier><identifier>DOI: 10.1016/j.jsbmb.2015.10.006</identifier><identifier>PMID: 26480216</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Caco-2 Cells - drug effects ; Cell Adhesion - genetics ; Cell Movement - genetics ; Cell Nucleus - metabolism ; Cell Proliferation - genetics ; Colon - metabolism ; Colon - physiopathology ; Dexamethasone - pharmacology ; Gene expression ; Gene Expression Regulation - drug effects ; Glucocorticoid receptor beta ; Glucocorticoid resistance ; Humans ; Inflammation ; Inflammatory bowel disease ; Inflammatory Bowel Diseases - genetics ; Inflammatory Bowel Diseases - physiopathology ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - physiopathology ; Receptors, Glucocorticoid - genetics ; Receptors, Glucocorticoid - metabolism ; Transcriptome</subject><ispartof>The Journal of steroid biochemistry and molecular biology, 2016-01, Vol.155 (Pt A), p.76-84</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c274t-efb9c4cd4c0dce4001faad7b3250065a67d8ef52ee7bb45e21b3d1a106800cd43</citedby><cites>FETCH-LOGICAL-c274t-efb9c4cd4c0dce4001faad7b3250065a67d8ef52ee7bb45e21b3d1a106800cd43</cites><orcidid>0000-0001-7506-674X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960076015301084$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26480216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagy, Zsolt</creatorcontrib><creatorcontrib>Acs, Bence</creatorcontrib><creatorcontrib>Butz, Henriett</creatorcontrib><creatorcontrib>Feldman, Karolina</creatorcontrib><creatorcontrib>Marta, Alexa</creatorcontrib><creatorcontrib>Szabo, Peter M.</creatorcontrib><creatorcontrib>Baghy, Kornelia</creatorcontrib><creatorcontrib>Pazmany, Tamas</creatorcontrib><creatorcontrib>Racz, Karoly</creatorcontrib><creatorcontrib>Liko, Istvan</creatorcontrib><creatorcontrib>Patocs, Attila</creatorcontrib><title>Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease</title><title>The Journal of steroid biochemistry and molecular biology</title><addtitle>J Steroid Biochem Mol Biol</addtitle><description>•GRß overexpression rendered Caco-2 cells steroid insensitive.•GRß was located in the nucleus and had an GRα independent transcriptional activity.•GRß regulated the expression of numerous involved in intact barrier function.
The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies.</description><subject>Caco-2 Cells - drug effects</subject><subject>Cell Adhesion - genetics</subject><subject>Cell Movement - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation - genetics</subject><subject>Colon - metabolism</subject><subject>Colon - physiopathology</subject><subject>Dexamethasone - pharmacology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucocorticoid receptor beta</subject><subject>Glucocorticoid resistance</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory Bowel Diseases - genetics</subject><subject>Inflammatory Bowel Diseases - physiopathology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - physiopathology</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Transcriptome</subject><issn>0960-0760</issn><issn>1879-1220</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UctOHDEQtCKisFnyBUjIRy6ztD3PPXBAiJBISEhRcrb86AleecaDPcuyn5ITH8OPxcMuKFIkTpbaVdVdVYQcM1gwYNXZarGKqlMLDqxMkwVA9YHMWFMvM8Y5HJAZLCvIoK7gkHyOcQUAec7qT-SQV0UDnFUz8uf2AQM-DgFjtL6nvqXXP56fqO2p9s73VtNurX2Ujmp0jjrbIx1kGN2WBmwd6jFS6cYkYuhvTJ__iP0nMskPcrTYJ9bGjncJ0jrZdXL0YUuV36CjxkaUEY_Ix1a6iF_275z8-nr18_JbdnN7_f3y4ibTvC7GDFu11IU2hQajsQBgrZSmVjkvUyClrGrTYFtyxFqpokTOVG6YZFA1AImWz8npTncI_n6NcRSdjZNX2aNfR8HqvCmavCnLBM13UB18jMm-GILtZNgKBmLqRKzESydi6mQaphMS62S_YK06NG-c1xIS4HwHwGTzwWIQUaeINBobUr7CePvugr-0AaNA</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>Nagy, Zsolt</creator><creator>Acs, Bence</creator><creator>Butz, Henriett</creator><creator>Feldman, Karolina</creator><creator>Marta, Alexa</creator><creator>Szabo, Peter M.</creator><creator>Baghy, Kornelia</creator><creator>Pazmany, Tamas</creator><creator>Racz, Karoly</creator><creator>Liko, Istvan</creator><creator>Patocs, Attila</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7506-674X</orcidid></search><sort><creationdate>201601</creationdate><title>Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease</title><author>Nagy, Zsolt ; Acs, Bence ; Butz, Henriett ; Feldman, Karolina ; Marta, Alexa ; Szabo, Peter M. ; Baghy, Kornelia ; Pazmany, Tamas ; Racz, Karoly ; Liko, Istvan ; Patocs, Attila</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c274t-efb9c4cd4c0dce4001faad7b3250065a67d8ef52ee7bb45e21b3d1a106800cd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Caco-2 Cells - drug effects</topic><topic>Cell Adhesion - genetics</topic><topic>Cell Movement - genetics</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation - genetics</topic><topic>Colon - metabolism</topic><topic>Colon - physiopathology</topic><topic>Dexamethasone - pharmacology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucocorticoid receptor beta</topic><topic>Glucocorticoid resistance</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory Bowel Diseases - genetics</topic><topic>Inflammatory Bowel Diseases - physiopathology</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestinal Mucosa - physiopathology</topic><topic>Receptors, Glucocorticoid - genetics</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagy, Zsolt</creatorcontrib><creatorcontrib>Acs, Bence</creatorcontrib><creatorcontrib>Butz, Henriett</creatorcontrib><creatorcontrib>Feldman, Karolina</creatorcontrib><creatorcontrib>Marta, Alexa</creatorcontrib><creatorcontrib>Szabo, Peter M.</creatorcontrib><creatorcontrib>Baghy, Kornelia</creatorcontrib><creatorcontrib>Pazmany, Tamas</creatorcontrib><creatorcontrib>Racz, Karoly</creatorcontrib><creatorcontrib>Liko, Istvan</creatorcontrib><creatorcontrib>Patocs, Attila</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagy, Zsolt</au><au>Acs, Bence</au><au>Butz, Henriett</au><au>Feldman, Karolina</au><au>Marta, Alexa</au><au>Szabo, Peter M.</au><au>Baghy, Kornelia</au><au>Pazmany, Tamas</au><au>Racz, Karoly</au><au>Liko, Istvan</au><au>Patocs, Attila</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease</atitle><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle><addtitle>J Steroid Biochem Mol Biol</addtitle><date>2016-01</date><risdate>2016</risdate><volume>155</volume><issue>Pt A</issue><spage>76</spage><epage>84</epage><pages>76-84</pages><issn>0960-0760</issn><eissn>1879-1220</eissn><abstract>•GRß overexpression rendered Caco-2 cells steroid insensitive.•GRß was located in the nucleus and had an GRα independent transcriptional activity.•GRß regulated the expression of numerous involved in intact barrier function.
The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26480216</pmid><doi>10.1016/j.jsbmb.2015.10.006</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7506-674X</orcidid></addata></record> |
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| subjects | Caco-2 Cells - drug effects Cell Adhesion - genetics Cell Movement - genetics Cell Nucleus - metabolism Cell Proliferation - genetics Colon - metabolism Colon - physiopathology Dexamethasone - pharmacology Gene expression Gene Expression Regulation - drug effects Glucocorticoid receptor beta Glucocorticoid resistance Humans Inflammation Inflammatory bowel disease Inflammatory Bowel Diseases - genetics Inflammatory Bowel Diseases - physiopathology Intestinal Mucosa - metabolism Intestinal Mucosa - physiopathology Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - metabolism Transcriptome |
| title | Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease |
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