High osmolality induces the kidney-specific chloride channel CLC-K1 by a serum and glucocorticoid-inducible kinase 1 MAPK pathway

The kidney-specific chloride channels CLC-K1/2 and their functionally important subunit barttin, by mediating solute transport in medulla, contribute to the osmotic gradient. We sought to determine whether they themselves are regulated by variations of osmolality. The expression of CLC-K1 and bartti...

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Bibliographic Details
Published in:Kidney international 2008-11, Vol.74 (9), p.1170-1177
Main Authors: Bergler, Tobias, Stoelcker, Benjamin, Jeblick, Roland, Reinhold, Stephan W., Wolf, Konrad, Riegger, Günter A.J., Krämer, Bernhard K.
Format: Article
Language:English
Subjects:
Animals
barttin
Biological and medical sciences
Cell Line
cell shrinkage
Chloride Channels - genetics
Gene Expression Regulation - physiology
Immediate-Early Proteins - genetics
Immediate-Early Proteins - metabolism
Kidney Tubules - cytology
Kidney Tubules - metabolism
Male
MAP Kinase Signaling System
Medical sciences
Membrane Proteins - genetics
Mice
Mice, Inbred C57BL
Nephrology. Urinary tract diseases
Osmolar Concentration
osmoregulation
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
RNA, Messenger - analysis
Up-Regulation - genetics
water deprivation
Water-Electrolyte Balance
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Summary:The kidney-specific chloride channels CLC-K1/2 and their functionally important subunit barttin, by mediating solute transport in medulla, contribute to the osmotic gradient. We sought to determine whether they themselves are regulated by variations of osmolality. The expression of CLC-K1 and barttin mRNA and protein was significantly increased in a distal convoluted tubule cell line after a shift to high osmolar medium. This upregulation paralleled that of serum and glucocorticoid-inducible kinase 1 (SGK1), a gene known to be upregulated by cell shrinkage. Specific knockdown of SGK1 or addition of the p38 MAPK pathway inhibitor SB203580 abolished the induction of SGK1, CLC-K1 and barttin by high osmolarity suggesting that a functional MAPK pathway is required to mediate osmotic-driven induction of all three genes. The physiological relevance of our in vitro data was confirmed by water deprivation of male C57BL6 mice, which caused a significant increase in serum osmolality along with induction of CLC-K1, barttin and SGK1. Our study shows that change in intracellular volume, because of high osmolality, result in SGK1 upregulation and the subsequent increase of CLC-K1/barttin expression in distal renal tubular cells in vivo and in vitro.
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.2008.312