Comment[ArrayExpressAccession]	E-GEOD-43416
MAGE-TAB Version	1.1							
Public Release Date	2013-02-28
Investigation Title	Gene Expression profiles of colon from Hif-2αF/F, Hif-2αlΔIE treated with DSS							
Comment[Submitted Name]	Gene Expression profiles of colon from Hif-2αF/F, Hif-2αlΔIE treated with DSS
Experiment Description	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).							
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl						
Person Last Name	XUE	Xue	Shah					
Person First Name	XIANG	Xiang	Yatrik					
Person Email	xxue@umich.edu							
Person Affiliation	Umich							
Person Address	Umich, 1301 E. Catherine Street, Ann Arbor, USA							
Person Roles	submitter							
Protocol Name	P-GSE43416-1	P-GSE43416-6	P-GSE43416-3	P-GSE43416-8	P-GSE43416-7	P-GSE43416-2	P-GSE43416-4	P-GSE43416-5
Protocol Description	ID_REF =  VALUE = Log 2 RMA normalized signal intensity	Following fragmentation, 16 ug of aRNA were hybridized for 16 hr at 45C on GeneChip Mouse 430 2.0 Array. GeneChips were washed and stained in the Affymetrix Fluidics Station 450.	All mice were C57BL/6 background and maintained in standard cages in a light and temperature-controlled room and were allowed standard chow and water ad libitum.	Data was analyzed using the affy Bioconductor packages implemented in the R-statistical environment. RMA was used to normalize the data and fit log2 transformed expression values.	GeneChips were scanned using the Affymetrix 3000 7G GeneChip Scanner with Autoloader.	Colon mucosal scrapings were got from 6 to 8 weeks old mice treated with 3% DSS for 3 days	Trizol extraction of total RNA was performed according to the manufacturer's instructions.	Biotinylated aRNA were prepared according to the Ambion Premier kit protocol from 250 ng total RNA (MessageAmp Premier RNA Amplification Kit Instruction Manual, 2008, Ambion).
Protocol Type	bioassay_data_transformation	hybridization	grow	feature_extraction	image_aquisition	specified_biomaterial_action	nucleic_acid_extraction	labeling
Experimental Factor Name	VARIATION							
Experimental Factor Type	variation							
Comment[SecondaryAccession]	GSE43416							
Comment[GEOReleaseDate]	2013-02-28							
Comment[ArrayExpressSubmissionDate]	2013-01-10							
Comment[GEOLastUpdateDate]	2013-03-01							
Comment[AEExperimentType]	transcription profiling by array							
SDRF File	E-GEOD-43416.sdrf.txt