title: The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion.
abstract: Aldosterone binds to the mineralocorticoid receptor (MR) and increases renal Na(+) reabsorption via up-regulation of the epithelial Na(+) channel (ENaC) and the Na(+)-K(+)-ATPase in the collecting system (CS) and possibly also via the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). However, whether aldosterone directly regulates NCC via MR or indirectly through systemic alterations remains controversial. We used mice with deletion of MR in ∼20 % of renal tubule cells (MR/X mice), in which MR-positive (MR(wt)) and -negative (MR(ko)) cells can be studied side-by-side in the same physiological context. Adult MR/X mice showed similar mRNA and protein levels of renal ion transport proteins to control mice. In MR/X mice, no differences in NCC abundance and phosphorylation was seen between MR(wt) and MR(ko) cells and dietary Na(+) restriction up-regulated NCC to similar extent in both groups of cells. In contrast, MR(ko) cells in the CS did not show any detectable alpha-ENaC abundance or apical targeting of ENaC neither on control diet nor in response to dietary Na(+) restriction. Furthermore, Na(+)-K(+)-ATPase expression was unaffected in MR(ko) cells of the DCT, while it was lost in MR(ko) cells of the CS. In conclusion, MR is crucial for ENaC and Na(+)-K(+)-ATPase regulation in the CS, but is dispensable for NCC and Na(+)-K(+)-ATPase regulation in the DCT.
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.|Swiss National Centre for Competence in Research "Kidney Control of Homeostasis", Zurich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Czogalla
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Twinkle
authors.initials: T
authors.lastname: Vohra
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.|Swiss National Centre for Competence in Research "Kidney Control of Homeostasis", Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Penton
authors.affiliation: Center for Microscopy and Image Analysis, University of Zurich, Zurich, Switzerland.
authors.forename: Moritz
authors.initials: M
authors.lastname: Kirschmann
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.|Swiss National Centre for Competence in Research "Kidney Control of Homeostasis", Zurich, Switzerland.
authors.forename: Eilidh
authors.initials: E
authors.lastname: Craigie
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. johannes.loffing@anatom.uzh.ch.|Swiss National Centre for Competence in Research "Kidney Control of Homeostasis", Zurich, Switzerland. johannes.loffing@anatom.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Loffing
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D049992:Sodium Chloride Symporters / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D018161:Receptors, Mineralocorticoid; D049992:Sodium Chloride Symporters; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Aldosterone; Distal tubule; Mineralocorticoid receptor; NCC