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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 07, 2018 |
| Title |
Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and integrity of the epithelium. The small ubiquitin-like modifier (SUMO) conjugation pathway critically regulates adaptive responses to metabolic stress and is of particular significance in the gut, as inducible knockout of the SUMO-conjugating enzyme Ubc9 results in rapid intestinal epithelial disintegration. Here we analyzed the pattern of individual SUMO isoforms in intestinal epithelium and investigated their roles in intestinal ischemia/reperfusion (I/R) damage. Immunostaining revealed that epithelial SUMO2/3 expression was almost exclusively limited to crypt epithelial nuclei in unchallenged mice. However, intestinal I/R or overexpression of Ubc9 caused a remarkable enhancement of epithelial SUMO2/3 staining along the crypt-villus axis. Unexpectedly, a similar pattern was found in SUMO1 knockout mice. Ubc9 transgenic mice, but also SUMO1 knockout mice were protected from I/R injury as evidenced by better preserved barrier function and blunted inflammatory responses. PCR array analysis of microdissected villus-tip epithelia revealed a specific epithelial contribution to reduced inflammatory responses in Ubc9 transgenic mice, as key chemotactic signaling molecules such as IL17A were significantly downregulated. Together, our data indicate a critical role particularly of the SUMO2/3 isoforms in modulating responses to I/R and provide the first evidence that SUMO1 deletion activates a compensatory process that protects from ischemic damage.
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| Overall design |
24 Mouse samples representing six groups with four replicates each: WT sham at 0hrs, Ubc9Tg sham at 0hrs, WT 45mins ischemia and 3hrs reperfusion, Ubc9Tg 45mins ischemia and 3hrs reperfusion, WT 45mins ischemia and 6hrs reperfusion, and Ubc9Tg 45mins ischemia and 6hrs reperfusion.
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| Contributor(s) |
Karhausen J, Bernstock JD, Johnson KR, Sheng H, Yang W, Hallenbeck JM, Paschen W |
| Citation(s) |
29472640 |
| Submission date |
Mar 16, 2017 |
| Last update date |
Feb 01, 2019 |
| Contact name |
Kory R Johnson |
| E-mail(s) |
johnsonko@ninds.nih.gov
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| Phone |
301-402-1956
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| Organization name |
NINDS/NIH
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| Department |
DIR IT & Bioinformatics
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| Lab |
Bioinformatics Section
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| Street address |
10/3B01, 9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA379474 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE96733_RAW.tar |
28.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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