Journal article
The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport
Proceedings of the National Academy of Sciences - PNAS, Vol.101(50), pp.17434-17439
12/14/2004
DOI: 10.1073/pnas.0408146101
PMCID: PMC536044
PMID: 15583131
Abstract
WNK1 belongs to a unique family of Ser/Thr kinases that have been implicated in the control of blood pressure. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. How overexpression of WNK1 leads to Na(+) retention and hypertension is not entirely clear. Similarly, there is no information on the hormonal regulation of expression of WNK kinases. There are two main WNK1 transcripts expressed in the kidney: the originally described "long" WNK1 and a shorter transcript that is specifically expressed in the kidney (KS-WNK1). The goal of this study was to determine the effect of aldosterone, the main hormonal regulator of Na(+) homeostasis, on the transcription of WNK1 isoforms in renal target cells, by using an unique mouse cortical collecting duct cell line that stably expresses functional mineralocorticoid receptors. Our results demonstrate that aldosterone, at physiological concentrations, rapidly induces the expression of the KS-WNK1 but not that of the long-WNK1 in these cells. Importantly, stable overexpression of KS-WNK1 significantly increases transepithelial Na(+) transport in cortical collecting duct cells. Similarly, coexpression of KS-WNK1 and the epithelial Na(+) channel in Fischer rat thyroid epithelial cells also stimulates Na(+) current, suggesting that KS-WNK1 affects the subcellular location or activity but not the expression of epithelial Na(+) channel. These observations suggest that stimulation of KS-WNK1 expression might be an important element of aldosterone-induced Na(+) retention and hypertension.
Details
- Title: Subtitle
- The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport
- Creators
- Anikó Náray-Fejes-Tóth - Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA. aniko-fejes-toth@dartmouth.eduPeter M SnyderGéza Fejes-Tóth
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.101(50), pp.17434-17439
- DOI
- 10.1073/pnas.0408146101
- PMID
- 15583131
- PMCID
- PMC536044
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences; United States
- Grant note
- R01 DK058898 / NIDDK NIH HHS R01 HL058812 / NHLBI NIH HHS DK 41841 / NIDDK NIH HHS R01 DK041841 / NIDDK NIH HHS HL 58812 / NHLBI NIH HHS DK 58898 / NIDDK NIH HHS R29 HL058812 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/14/2004
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984025688002771
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