The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion
Standard
The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion. / Czogalla, Jan; Vohra, Twinkle; Penton, David; Kirschmann, Moritz; Craigie, Eilidh; Loffing, Johannes.
in: PFLUG ARCH EUR J PHY, Jahrgang 468, Nr. 5, 05.2016, S. 849-58.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion
AU - Czogalla, Jan
AU - Vohra, Twinkle
AU - Penton, David
AU - Kirschmann, Moritz
AU - Craigie, Eilidh
AU - Loffing, Johannes
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
KW - Aldosterone
KW - Animals
KW - Epithelial Sodium Channels
KW - Female
KW - Gene Deletion
KW - Kidney Tubules, Distal
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Receptors, Mineralocorticoid
KW - Sodium
KW - Sodium Chloride Symporters
KW - Sodium Chloride, Dietary
KW - Sodium-Potassium-Exchanging ATPase
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00424-016-1798-5
DO - 10.1007/s00424-016-1798-5
M3 - SCORING: Journal article
C2 - 26898302
VL - 468
SP - 849
EP - 858
JO - PFLUG ARCH EUR J PHY
JF - PFLUG ARCH EUR J PHY
SN - 0031-6768
IS - 5
ER -