Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease
| Autor: | Alexa Marta, Karolina Feldman, Zsolt Nagy, Károly Rácz, Attila Patócs, Bence Acs, Henriett Butz, Kornélia Baghy, Péter Szabó, István Likó, Tamas Pazmany |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Microarray Colon Endocrinology Diabetes and Metabolism Clinical Biochemistry Biology Biochemistry Inflammatory bowel disease Dexamethasone Transcriptome 03 medical and health sciences Endocrinology Glucocorticoid receptor Receptors Glucocorticoid Intestinal mucosa Cell Movement Gene expression medicine Cell Adhesion Humans Intestinal Mucosa Molecular Biology Cell Proliferation Regulation of gene expression Cell Nucleus fungi Cell Biology medicine.disease Inflammatory Bowel Diseases Intestinal epithelium 030104 developmental biology Gene Expression Regulation Immunology Cancer research Molecular Medicine Caco-2 Cells |
| Zdroj: | The Journal of steroid biochemistry and molecular biology. 155 |
| ISSN: | 1879-1220 |
| Popis: | 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 GRs. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRs may have a GRα-independent transcriptional activity. The GRs 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 GRs overexpressing intestinal cell line (Caco-2GRs) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRs 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 GRs altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRs 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 GRs intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRs in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRs in intestinal epithelium warrants further studies. |
| Databáze: | OpenAIRE |
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