{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSM106223": {"VARIATION": "Hif-2\u03b1F/F"}}, {"GSM1062232": {"VARIATION": "Hif-2\u03b1\u0394IE"}}], "id": 7131, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "To investigate the detailed molecular mechanisms for the regulatory role of HIF-2\u03b1 in experimental colitis, microarray gene expression...", "geo_gse_id": "E-GEOD-43416", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 2, "tags": ["colitis", "colon", "disease", "dss", "ibd", "inflammatory bowel disease", "intestinal epithelium", "intestine"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-43416_A-AFFY-45", "slug": "gene-expression-profiles-of-colon-from-hif-2ff-hif", "geo_gds_id": "", "name": "Gene Expression profiles of colon from Hif-2\u03b1F/F, Hif-2\u03b1l\u0394IE treated with DSS", "created": "Nov.12, 2014", "summary": "To investigate the detailed molecular mechanisms for the regulatory role of HIF-2\u03b1 in experimental colitis, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-2\u03b1F/F, Hif-2\u03b1l\u0394IE mice treated with 3%DSS for 3 days. Background & Aims: Hypoxic inflammation is characterized by decreased oxygen tension in inflammatory foci, and is a notable feature in inflammatory bowel disease (IBD). Hypoxic response is mediated by transcription factors hypoxia-inducible factor (HIF)-1\u03b1 and HIF-2\u03b1, both of which are highly induced in IBD. HIF-1\u03b1 is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF-2\u03b1 has not been assessed in hypoxic inflammation and IBD.   Methods: A hypoxia reporter mouse model was used to test the presence of hypoxia and HIF-2\u03b1 in dextran sulfate sodium (DSS) and Citrobacter rodentium (C.rod)-induced colitis. The role of HIF-2\u03b1 in these mouse models of colitis was further assessed in mice with an intestinal epithelium-specific gain- and loss-of-function of HIF-2\u03b1.   Results: Induction of hypoxia and HIF-2\u03b1 was confirmed in both murine experimental colitis models and human IBD samples. Disruption of HIF-2\u03b1 attenuated colonic inflammation whereas stabilization of HIF-2\u03b1 potentiated inflammation in mouse models of colitis. Interestingly, intestine specific overexpression of HIF-2\u03b1 but not HIF-1\u03b1 leads to spontaneous colitis and premature death in mice. Further mechanistic analysis showed that HIF-2\u03b1 is a driver for pro-inflammatory response and is critical regulator of intestinal epithelial-derived tumor necrosis factor (TNF)-\u03b1. Blocking TNF-\u03b1 completely ameliorated HIF-2\u03b1 potentiated intestinal inflammation.   Conclusions: These data demonstrate that HIF-2\u03b1 is a critical transcription factor essential in intestinal epithelium elicited inflammatory response. Global gene expression profiling in colon RNAs isolated from 7-week-old Hif-2\u03b1F/F (n=6, Shah 007) and Hif-2\u03b1\u0394IE (n=5, Shah 008).", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43416", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43416/samples/"}