Deletion of the serine protease CAP2/Tmprss4 leads to dysregulated renal water handling upon dietary potassium depletion.

Détails

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Etat: Public
Version: de l'auteur
Licence: CC BY 4.0
ID Serval
serval:BIB_38624B0769FD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Deletion of the serine protease CAP2/Tmprss4 leads to dysregulated renal water handling upon dietary potassium depletion.
Périodique
Scientific reports
Auteur(s)
Keppner A., Maric D., Sergi C., Ansermet C., De Bellis D., Kratschmar D.V., Canonica J., Klusonova P., Fenton R.A., Odermatt A., Crambert G., Hoogewijs D., Hummler E.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
20/12/2019
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
19540
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
The kidney needs to adapt daily to variable dietary K <sup>+</sup> contents via various mechanisms including diuretic, acid-base and hormonal changes that are still not fully understood. In this study, we demonstrate that following a K <sup>+</sup> -deficient diet in wildtype mice, the serine protease CAP2/Tmprss4 is upregulated in connecting tubule and cortical collecting duct and also localizes to the medulla and transitional epithelium of the papilla and minor calyx. Male CAP2/Tmprss4 knockout mice display altered water handling and urine osmolality, enhanced vasopressin response leading to upregulated adenylate cyclase 6 expression and cAMP overproduction, and subsequently greater aquaporin 2 (AQP2) and Na <sup>+</sup> -K <sup>+</sup> -2Cl <sup>-</sup> cotransporter 2 (NKCC2) expression following K <sup>+</sup> -deficient diet. Urinary acidification coincides with significantly increased H <sup>+</sup> ,K <sup>+</sup> -ATPase type 2 (HKA2) mRNA and protein expression, and decreased calcium and phosphate excretion. This is accompanied by increased glucocorticoid receptor (GR) protein levels and reduced 11β-hydroxysteroid dehydrogenase 2 activity in knockout mice. Strikingly, genetic nephron-specific deletion of GR leads to the mirrored phenotype of CAP2/Tmprss4 knockouts, including increased water intake and urine output, urinary alkalinisation, downregulation of HKA2, AQP2 and NKCC2. Collectively, our data unveil a novel role of the serine protease CAP2/Tmprss4 and GR on renal water handling upon dietary K <sup>+</sup> depletion.
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/01/2020 15:59
Dernière modification de la notice
11/02/2020 6:19
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