Mederle, Katharina and Mutig, Kerim and Paliege, Alexander and Carota, Isabel and Bachmann, Sebastian and Castrop, Hayo and Oppermann, Mona (2013) Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 304 (9). F1198-F1209. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
WNK3 kinase is expressed throughout the nephron and acts as a positive regulator of NKCC2 and NCC in vitro. Here we addressed the in vivo relevance of WNK3 using WNK3-deficient mice. WNK3-/- mice were viable and showed no gross abnormalities. The net tubular function was similar in wild-type (WT) and WNK3-/- mice as assessed by determination of 24-h urine output (1.63 +/- .06 in WT and 1.55 +/- center dot 1 ml in WNK3-/-, n=16; P=0.42) and ambient urine osmolarity (1,804 +/- 62 in WT vs. 1,819 +/- 61 mosmol/kg in WNK3-/-, n=40; P=0.86). Water restriction (48 h) increased urine osmolarity similarly in both genotypes to 3,440 +/- 220 and 3,200 +/- 180 mosmol/kg in WT and WNK3-/- mice, respectively (n=11; P=0.41). The glomerular filtration rate (343 +/- 22 vs. 315 +/- 13 ml/min), renal blood flow (1.35 +/- 0.1 vs. 1.42 +/- 0.04 ml), and plasma renin concentration (94 +/- 18 vs. 80 +/- 13 ng ANG I center dot ml(-1) center dot h(-1)) were similar between WT and WNK3-/- mice (n=13; P=0.54). WNK1 was markedly upregulated in WNK3-deficient mice, whereas the expression of WNK4 was similar in both genotypes. When the mice were fed a salt-restricted diet [0.02% NaCl (wt/wt)] the levels of pSPAK/OSR1, pNKCC2, and pNCC were enhanced in both genotypes compared with the baseline conditions, with the levels in WNK3-/- exceeding those in WT mice. The upregulation of pSPAK/OSR1, pNKCC2, and pNCC in WNK3-/- mice relative to the levels in WT mice when fed a low-salt diet was paralleled by an increased diuresis in response to hydrochlorothiazide. In summary, the overall relevance of WNK3 for the renal reabsorption of NaCl appears to be limited and can be largely compensated for by the activation of WNK3-independent pathways. Consequently, our data suggest that WNK3 may serve as a member of a kinase network that facilitates the fine-tuning of renal transepithelial NaCl transport.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NA-CL COTRANSPORTER; BLOOD-PRESSURE; ACIDIC MOTIF; KINASE; HYPERTENSION; EXPRESSION; NCC; ISOFORM; SODIUM; NKCC2; kidney; NKCC2; NCC; tubular function; WNK1; WNK3 |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2020 13:13 |
| Last Modified: | 09 Apr 2020 13:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16717 |
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