Transcriptomics

Dataset Information

4

Gene Expression profiles of colon from Hif-2αF/F, Hif-2αlΔIE treated with DSS


ABSTRACT: To investigate the detailed molecular mechanisms for the regulatory role of HIF-2α in experimental colitis, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-2αF/F, Hif-2αlΔIE 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)-1α and HIF-2α, both of which are highly induced in IBD. HIF-1α is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF-2α 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-2α in dextran sulfate sodium (DSS) and Citrobacter rodentium (C.rod)-induced colitis. The role of HIF-2α in these mouse models of colitis was further assessed in mice with an intestinal epithelium-specific gain- and loss-of-function of HIF-2α. Results: Induction of hypoxia and HIF-2α was confirmed in both murine experimental colitis models and human IBD samples. Disruption of HIF-2α attenuated colonic inflammation whereas stabilization of HIF-2α potentiated inflammation in mouse models of colitis. Interestingly, intestine specific overexpression of HIF-2α but not HIF-1α leads to spontaneous colitis and premature death in mice. Further mechanistic analysis showed that HIF-2α is a driver for pro-inflammatory response and is critical regulator of intestinal epithelial-derived tumor necrosis factor (TNF)-α. Blocking TNF-α completely ameliorated HIF-2α potentiated intestinal inflammation. Conclusions: These data demonstrate that HIF-2α 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-2αF/F (n=6, Shah 007) and Hif-2αΔIE (n=5, Shah 008).

ORGANISM(S): Mus musculus  

SUBMITTER: XIANG XUE   Yatrik Shah  Xiang Xue 

PROVIDER: E-GEOD-43416 | ArrayExpress | 2013-02-28

SECONDARY ACCESSION(S): GSE43416PRJNA186026

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2012-03-07 | E-GEOD-36091 | ArrayExpress
2014-05-14 | E-GEOD-55915 | ArrayExpress
2010-06-28 | GSE22575 | GEO
2010-07-29 | E-GEOD-22575 | ArrayExpress
2015-07-24 | E-GEOD-59729 | ArrayExpress
2015-07-24 | E-GEOD-55212 | ArrayExpress
2016-03-22 | E-GEOD-70727 | ArrayExpress
2014-07-03 | E-GEOD-22575 | ExpressionAtlas
| GSE54360 | GEO
2014-05-14 | E-GEOD-57613 | ArrayExpress