Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/122750
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dc.contributor.author | Manning, J.A. | - |
dc.contributor.author | Shah, S.S. | - |
dc.contributor.author | Henshall, T.L. | - |
dc.contributor.author | Nikolic, A. | - |
dc.contributor.author | Finnie, J. | - |
dc.contributor.author | Kumar, S. | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Cell Death and Differentiation, 2020; 27(6):1832-1843 | - |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.issn | 1476-5403 | - |
dc.identifier.uri | http://hdl.handle.net/2440/122750 | - |
dc.description.abstract | Salt homeostasis is maintained by tight control of Na+ filtration and reabsorption. In the distal part of the nephron the ubiquitin protein ligase Nedd4-2 regulates membrane abundance and thus activity of the epithelial Na+ channel (ENaC), which is rate-limiting for Na+ reabsorption. Nedd4-2 deficiency in mouse results in elevated ENaC and nephropathy, however the contribution of dietary salt to this has not been characterized. In this study we show that high dietary Na+ exacerbated kidney injury in Nedd4-2-deficient mice, significantly perturbing normal postnatal nephrogenesis and resulting in multifocal areas of renal dysplasia, increased markers of kidney injury and a decline in renal function. In control mice, high dietary Na+ resulted in reduced levels of ENaC. However, Nedd4-2-deficient kidneys maintained elevated ENaC even after high dietary Na+, suggesting that the inability to efficiently downregulate ENaC is responsible for the salt-sensitivity of disease. Importantly, low dietary Na+ significantly ameliorated nephropathy in Nedd4-2-deficient mice. Our results demonstrate that due to dysregulation of ENaC, kidney injury in Nedd4-2-deficient mice is sensitive to dietary Na+, which may have implications in the management of disease in patients with kidney disease. | - |
dc.description.statementofresponsibility | Jantina A. Manning, Sonia S. Shah, Tanya L. Henshall, Andrej Nikolic, John Finnie and Sharad Kumar | - |
dc.language.iso | en | - |
dc.publisher | Nature | - |
dc.rights | © The Author(s) 2019. This article is published with open access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | - |
dc.source.uri | http://dx.doi.org/10.1038/s41418-019-0468-5 | - |
dc.subject | Kidney diseases; ubiquitin ligases | - |
dc.title | Dietary sodium modulates nephropathy in Nedd4-2-deficient mice | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/s41418-019-0468-5 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/GNT1103006 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/GNT1099307 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Finnie, J. [0000-0003-2277-1693] | - |
dc.identifier.orcid | Kumar, S. [0000-0001-7126-9814] | - |
Appears in Collections: | Aurora harvest 8 Biochemistry publications |
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hdl_122750.pdf | Published version | 3.99 MB | Adobe PDF | View/Open |
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