Elevated serum magnesium lowers calcification propensity in Memo1-deficient mice

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_8EEA005448A4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Elevated serum magnesium lowers calcification propensity in Memo1-deficient mice
Journal
PLOS ONE
Author(s)
Moor Matthias B., Ramakrishnan Suresh K., Legrand Finola, Bachtler Matthias, Koesters Robert, Hynes Nancy E., Pasch Andreas, Bonny Olivier
ISSN
1932-6203
ISSN-L
1932-6203
Publication state
Published
Issued date
24/07/2020
Peer-reviewed
Oui
Volume
15
Number
7
Pages
e0236361
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
MEdiator of cell MOtility1 (MEMO1) is a ubiquitously expressed redox protein involved in extracellular ligand-induced cell signaling. We previously reported that inducible whole-body Memo1 KO (cKO) mice displayed a syndrome of premature aging and disturbed mineral metabolism partially recapitulating the phenotype observed in Klotho or Fgf23-deficient mouse models. Here, we aimed at delineating the contribution of systemic mineral load on the Memo1 cKO mouse phenotype. We attempted to rescue the Memo1 cKO phenotype by depleting phosphate or vitamin D from the diet, but did not observe any effect on survival. However, we noticed that, by contrast to Klotho or Fgf23-deficient mouse models, Memo1 cKO mice did not present any soft-tissue calcifications and displayed even a decreased serum calcification propensity. We identified higher serum magnesium levels as the main cause of protection against calcifications. Expression of genes encoding intestinal and renal magnesium channels and the regulator epidermal growth factor were increased in Memo1 cKO. In order to check whether magnesium reabsorption in the kidney alone was driving the higher magnesemia, we generated a kidney-specific Memo1 KO (kKO) mouse model. Memo1 kKO mice also displayed higher magnesemia and increased renal magnesium channel gene expression. Collectively, these data identify MEMO1 as a novel regulator of magnesium homeostasis and systemic calcification propensity, by regulating expression of the main magnesium channels.
Keywords
General Biochemistry, Genetics and Molecular Biology, General Agricultural and Biological Sciences, General Medicine
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation
Create date
11/08/2020 10:48
Last modification date
20/01/2021 7:09
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