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The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion

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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, Vol. 468, No. 5, 05.2016, p. 849-58.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Czogalla, J, Vohra, T, Penton, D, Kirschmann, M, Craigie, E & Loffing, J 2016, 'The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion', PFLUG ARCH EUR J PHY, vol. 468, no. 5, pp. 849-58. https://doi.org/10.1007/s00424-016-1798-5

APA

Czogalla, J., Vohra, T., Penton, D., Kirschmann, M., Craigie, E., & Loffing, J. (2016). The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion. PFLUG ARCH EUR J PHY, 468(5), 849-58. https://doi.org/10.1007/s00424-016-1798-5

Vancouver

Czogalla J, Vohra T, Penton D, Kirschmann M, Craigie E, Loffing J. The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion. PFLUG ARCH EUR J PHY. 2016 May;468(5):849-58. https://doi.org/10.1007/s00424-016-1798-5

Bibtex

@article{696aaa4319e9407493f429377e467e00,
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.",
keywords = "Aldosterone, Animals, Epithelial Sodium Channels, Female, Gene Deletion, Kidney Tubules, Distal, Male, Mice, Mice, Inbred C57BL, Receptors, Mineralocorticoid, Sodium, Sodium Chloride Symporters, Sodium Chloride, Dietary, Sodium-Potassium-Exchanging ATPase, Journal Article, Research Support, Non-U.S. Gov't",
author = "Jan Czogalla and Twinkle Vohra and David Penton and Moritz Kirschmann and Eilidh Craigie and Johannes Loffing",
year = "2016",
month = may,
doi = "10.1007/s00424-016-1798-5",
language = "English",
volume = "468",
pages = "849--58",
journal = "PFLUG ARCH EUR J PHY",
issn = "0031-6768",
publisher = "Springer",
number = "5",

}

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 -