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unige:1261 
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Aldosterone activates NF-kappaB in the collecting duct |
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| Authors | ||
| 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 Nucleus — Aldosterone/pharmacology — Animals — Cells, Cultured — Extracellular Signal-Regulated MAP Kinases/physiology — I-kappa B Kinase/physiology — I-kappa B Proteins/physiology — Immediate-Early Proteins/physiology — Kidney Tubules, Collecting/metabolism — Male — NF-kappa B/metabolism — Phosphorylation — Protein-Serine-Threonine Kinases/physiology — Rats — Rats, Sprague-Dawley — Receptors, Mineralocorticoid/drug effects/physiology — Sodium Chloride, Dietary/administration & dosage — Transcription Factor RelA/metabolism — P38 Mitogen-Activated Protein Kinases/physiology | |
| Stable URL | https://archive-ouverte.unige.ch/unige:1261 | |
| Full text |
Article (Author postprint) (684 Kb) - Limited access to UNIGE Other version: http://jasn.asnjournals.org/cgi/content/full/20/1/131 |
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| Identifiers |
PMID: 18987305 |
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| Structures | ||
| Research groups | Groupe Eric Féraille (néphrologie) (29) Groupe Pierre-Yves Martin (néphrologie) (30) Obésité et syndrome métabolique (803) |
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