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The Inflammatory Transcription Factors NF?B, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney.

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. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NF?B, STAT1 and STAT3, the activities of which increase 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? (a STAT1 activator), or TNF? (an NF?B activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NF?B transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NF?B contributes to renal aging phenotypes. Our results suggest that NF?B, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney.

SUBMITTER: O'Brown ZK

PROVIDER: S-EPMC4682820 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney.

O'Brown Zach K ZK Van Nostrand Eric L EL Higgins John P JP Kim Stuart K SK

PLoS genetics 20151217 12

Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, t ...[more]

PMID: 26678048

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The Inflammatory Transcription Factors NF?B, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney.

Publications

The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney.

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