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Aldosterone Activates NF-κB in the Collecting Duct
- Source :
- Journal of the American Society of Nephrology, Vol. 20, No 1 (2009) pp. 131-144
- Publication Year :
- 2009
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2009.
-
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.
- Subjects :
- Male
Transcription Factor RelA/metabolism
Extracellular Signal-Regulated MAP Kinases/physiology
p38 Mitogen-Activated Protein Kinases
Rats, Sprague-Dawley
chemistry.chemical_compound
Transactivation
Mineralocorticoid receptor
Glucocorticoid receptor
NF-KappaB Inhibitor alpha
Protein-Serine-Threonine Kinases/physiology
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Aldosterone
Cells, Cultured
ddc:616
NF-kappa B
General Medicine
I-kappa B Kinase
Immediate-Early Proteins/physiology
Nephrology
I-kappa B Proteins
Signal transduction
I-kappa B Kinase/physiology
Kidney Tubules, Collecting/metabolism
medicine.medical_specialty
medicine.drug_class
Active Transport, Cell Nucleus
Aldosterone/pharmacology
Protein Serine-Threonine Kinases
Biology
Immediate-Early Proteins
Internal medicine
Sodium Chloride, Dietary/administration & dosage
medicine
Animals
Kidney Tubules, Collecting
Sodium Chloride, Dietary
ddc:612
Transcription Factor RelA
Rats
Receptors, Mineralocorticoid
Basic Research
Endocrinology
chemistry
Mineralocorticoid
Receptors, Mineralocorticoid/drug effects/physiology
NF-kappa B/metabolism
I-kappa B Proteins/physiology
SGK1
P38 Mitogen-Activated Protein Kinases/physiology
Homeostasis
Subjects
Details
- ISSN :
- 10466673
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....ebf97aada509f413b6689611bf0d064b