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Tubular epithelial NF-κB activity regulates acute ischemic kideny injury

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE87025 | GEO | 2016/09/17

SECONDARY ACCESSION(S): PRJNA343239

REPOSITORIES: GEO

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Tubular epithelial NF-κB activity regulates acute ischemic kideny injury [OTT-211009]

Project description:NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of acute kidney injury (AKI). The cell type-specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue-parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed widespread NF-κB activation in renal tubular epithelia and in interstitial cells following IRI that peaked at 2-3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBα∆N in renal proximal, distal, and collecting duct epithelial cells. These mice were protected from IRI-induced AKI, as indicated by improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration. Tubular NF-κB-dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBα∆N-expressing mice exposed to hypoxia-mimetic agent cobalt chloride were protected from apoptosis and expressed reduced levels of chemokines. Our results indicate that postischemic NF-κB activation in renal-tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.

2016-09-17 | GSE87024 | GEO

Tubular epithelial NF-κB activity regulates acute ischemic kideny injury [130402-EV-EmxdN]

2016-09-17 | GSE87023 | GEO

Tubular epithelial NF-κB activity regulates acute ischemic kideny injury

Project description:Tubular epithelial NF-κB activity regulates acute ischemic kideny injury

| PRJNA343239 | ENA

Tubular Epithelial NF-?B Activity Regulates Ischemic AKI.