en
Scientific article
English

Aldosterone activates NF-kappaB in the collecting duct

Published inJournal of the American Society of Nephrology, vol. 20, no. 1, p. 131-144
Publication date2009
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
Citation (ISO format)
LEROY, Valérie et al. Aldosterone activates NF-kappaB in the collecting duct. In: Journal of the American Society of Nephrology, 2009, vol. 20, n° 1, p. 131–144. doi: 10.1681/ASN.2008020232
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal1046-6673
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Creation30.03.2009 16:25:00
First validation30.03.2009 16:25:00
Update time14.03.2023 15:03:48
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