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Title: Response of HK-2 cells to stimulation with IL6 and TNF-alpha (90 minutes)      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
08-19-2015
ID:
E-GEOD-68940
description:
Abstract: Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. We compared age-associated changes in global gene expression patterns in the human kidney with genome-wide maps of transcription factor occupancy in human cell lines to identify potential regulators of gene expression changes in the aging kidney. The strongest associations involved three inflammation-associated transcription factors: NFκB, STAT1 and STAT3. We found that the activity of these transcription factors increases with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFN-γ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We found that common DNA variants in the two genes that encode the subunits of the canonical NFκB transcription factor (RELA and NFKB1) showed significant associations with kidney function and chronic kidney disease in gene association studies, providing the first evidence for a direct link between genetic variation in NFκB and individual differences in age-related phenotypes in the kidney. Our results point to chronic inflammation, mediated by NFκB, STAT1 and STAT3, as a dominant mechanism influencing gene expression changes during kidney aging. Biological triplicate experiments were performed for each cytokine treatment condition or control treatment.
keywords:
transcription profiling by array
format:
HTML
storedIn:
Array Express
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not compressed
accessType:
landing page
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primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-68940
format:
JSON
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
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none
authentication:
none
primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-68940.json
format:
XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-68940.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/

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