NF-kappaB inhibits sodium transport via down-regulation of SGK1 in renal collecting duct principal cells.

Details

Serval ID
serval:BIB_2E6AE9836372
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
NF-kappaB inhibits sodium transport via down-regulation of SGK1 in renal collecting duct principal cells.
Journal
Journal of Biological Chemistry
Author(s)
de Seigneux S., Leroy V., Ghzili H., Rousselot M., Nielsen S., Rossier B.C., Martin P.Y., Féraille E.
ISSN
0021-9258
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
283
Number
37
Pages
25671-25681
Language
english
Abstract
Tubulointerstitial inflammation is a common feature of renal diseases. We have investigated the relationship between inflammation and Na(+) transport in the collecting duct (CD) using the mCCD(cl1) and mpkCDD(cl4) principal cell models. Lipopolysaccharide (LPS) decreased basal and aldosterone-stimulated amiloride-sensitive transepithelial current in a time-dependent manner. This effect was associated with a decrease in serum and glucocorticoid-regulated kinase 1 (SGK1) mRNA and protein levels followed by a decrease in epithelial sodium channel (ENaC) alpha-subunit mRNA levels. The LPS-induced decrease in SGK1 expression was confirmed in isolated rat CD. This decreased expression of either SGK1 or the ENaC alpha-subunit was not due to enhanced degradation of mRNA. In contrast, LPS inhibited transcriptional activity of the SGK1 promoter measured by luciferase-reporter gene assay. The effect of LPS was not mediated by inhibition of mineralocorticoid or glucocorticoid receptor, because expression of both receptors was unchanged and blockade of either receptor by spironolactone or RU486, respectively, did not prevent the down-regulation of SGK1. The effect of LPS was mediated by the canonical NF-kappaB pathway, as overexpression of a constitutively active mutant, IKKbeta (inhibitor of nuclear factor kappaB kinase-beta) decreased SGK1 mRNA levels, and knockdown of p65 NF-kappaB subunit by small interfering RNA increased SGK1 mRNA levels. Chromatin immunoprecipitation showed that LPS increased p65 binding to two NF-kappaB sites along the SGK1 promoter. In conclusion, we show that activation of the NF-kappaB pathway down-regulates SGK1 expression, which might lead to decreased ENaC alpha-subunit expression, ultimately resulting in decreased Na(+) transport.
Keywords
Animals, Biological Transport, Down-Regulation, Epithelial Sodium Channel/metabolism, Immediate-Early Proteins/metabolism, Immediate-Early Proteins/physiology, Kidney Tubules, Collecting/metabolism, Male, Mice, Models, Biological, NF-kappa B/metabolism, Protein-Serine-Threonine Kinases/metabolism, Protein-Serine-Threonine Kinases/physiology, RNA, Messenger/metabolism, Rats, Rats, Sprague-Dawley, Sodium/chemistry, Sodium/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
29/10/2009 16:09
Last modification date
23/11/2020 11:07
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