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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 28, 2013 |
| Title |
Gene Expression profiles of colon from Hif-2αF/F, Hif-2αlΔIE treated with DSS |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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).
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| Contributor(s) |
Xue X, Shah Y |
| Citation(s) |
23860500 |
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| Submission date |
Jan 10, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
XIANG XUE |
| E-mail(s) |
[email protected]
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| Phone |
7346155041
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| Organization name |
Umich
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| Street address |
1301 E. Catherine Street
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| City |
Ann Arbor |
| State/province |
Michigan |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA186026 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43416_RAW.tar |
7.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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