title: Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease.
abstract: 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.
authors.affiliation: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; Hungarian Academy of Sciences-Semmelweis University "Lendulet" Hereditary Endocrine Tumors Research Group, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Nagy
authors.affiliation: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Acs
authors.affiliation: Hungarian Academy of Sciences-Semmelweis University "Lendulet" Hereditary Endocrine Tumors Research Group, Budapest, Hungary; Hungarian Academy of Sciences-Semmelweis University Molecular Medicine Research Group, Budapest, Hungary.
authors.forename: Henriett
authors.initials: H
authors.lastname: Butz
authors.affiliation: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Karolina
authors.initials: K
authors.lastname: Feldman
authors.affiliation: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Alexa
authors.initials: A
authors.lastname: Marta
authors.affiliation: Hungarian Academy of Sciences-Semmelweis University Molecular Medicine Research Group, Budapest, Hungary.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Szabo
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Baghy
authors.affiliation: Gedeon Richter PLC, Budapest, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Pazmany
authors.affiliation: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; Hungarian Academy of Sciences-Semmelweis University Molecular Medicine Research Group, Budapest, Hungary.
authors.forename: Karoly
authors.initials: K
authors.lastname: Racz
authors.affiliation: Hungarian Academy of Sciences-Semmelweis University "Lendulet" Hereditary Endocrine Tumors Research Group, Budapest, Hungary; Gedeon Richter PLC, Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Liko
authors.affiliation: Hungarian Academy of Sciences-Semmelweis University "Lendulet" Hereditary Endocrine Tumors Research Group, Budapest, Hungary; Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary. Electronic address: patocs.attila@med.semmelweis-univ.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Patocs
mesh_terms: D018938:Caco-2 Cells / Q000187:drug effects; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D003106:Colon / Q000378:metabolism / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta; D003907:Dexamethasone
keywords: Gene expression; Glucocorticoid receptor beta; Glucocorticoid resistance; Inflammation; Inflammatory bowel disease