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Title

Aldosterone activates NF-kappaB in the collecting duct

Authors
de Seigneux, Sophie
Agassiz, Victor
Rafestin-Oblin, Marie-Edith
Published in Journal of the American Society of Nephrology. 2009, vol. 20, no. 1, p. 131-144
Abstract Besides its classical effects on salt homeostasis in renal epithelial cells, aldosterone promotes inflammation and fibrosis and modulates cell proliferation. The proinflammatory transcription factor NF-kappaB has been implicated in cell proliferation, apoptosis, and regulation of transepithelial sodium transport. The effect of aldosterone on the NF-kappaB pathway in principal cells of the cortical collecting duct, a major physiologic target of aldosterone, is unknown. Here, in both cultured cells and freshly isolated rat cortical collecting duct, aldosterone activated the canonical NF-kappaB signaling pathway, leading to increased expression of several NF-kappaB-targeted genes (IkappaBalpha, plasminogen activator inhibitor 1, monocyte chemoattractant protein 1, IL-1beta, and IL-6). Small interfering RNA-mediated knockdown of the serum and glucocorticoid-inducible kinase SGK1, a gene induced early in the response to aldosterone, but not pharmacologic inhibition of extracellular signal-regulated kinase and p38 kinase, attenuated aldosterone-induced NF-kappaB activation. Pharmacologic antagonism or knockdown of the mineralocorticoid receptor prevented aldosterone-induced NF-kappaB activity. In addition, activation of the glucocorticoid receptor inhibited the transactivation of NF-kappaB by aldosterone. In agreement with these in vitro findings, spironolactone prevented NF-kappaB-induced transcriptional activation observed in cortical collecting ducts of salt-restricted rats. In summary, aldosterone activates the canonical NF-kappaB pathway in principal cells of the cortical collecting duct by activating the mineralocorticoid receptor and by inducing SGK1.
Keywords Active Transport, Cell NucleusAldosterone/pharmacologyAnimalsCells, CulturedExtracellular Signal-Regulated MAP Kinases/physiologyI-kappa B Kinase/physiologyI-kappa B Proteins/physiologyImmediate-Early Proteins/physiologyKidney Tubules, Collecting/metabolismMaleNF-kappa B/metabolismPhosphorylationProtein-Serine-Threonine Kinases/physiologyRatsRats, Sprague-DawleyReceptors, Mineralocorticoid/drug effects/physiologySodium Chloride, Dietary/administration & dosageTranscription Factor RelA/metabolismP38 Mitogen-Activated Protein Kinases/physiology
Stable URL http://archive-ouverte.unige.ch/unige:1261
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Identifiers
PMID: 18987305
Structures
Research groups Groupe Eric Féraille (néphrologie) (29)
Groupe Pierre-Yves Martin (néphrologie) (30)
Obésité et syndrome métabolique (803)

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Deposited on : 2009-03-30

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