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

Details

Ressource 1Request a copy Sous embargo indéterminé.
State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_38624B0769FD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Deletion of the serine protease CAP2/Tmprss4 leads to dysregulated renal water handling upon dietary potassium depletion.
Journal
Scientific reports
Author(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
Publication state
Published
Issued date
20/12/2019
Peer-reviewed
Oui
Volume
9
Number
1
Pages
19540
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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
Yes
Create date
03/01/2020 15:59
Last modification date
17/09/2020 8:13
Usage data