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NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression

The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions, such as myopathies. Here, we investigated whether the nuclear receptor subfamily 1 group D member (NR1D1, also called REV-ERBα) regulates skeletal muscle SR...

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Autores principales: Boulinguiez, Alexis, Duhem, Christian, Mayeuf-Louchart, Alicia, Pourcet, Benoit, Sebti, Yasmine, Kondratska, Kateryna, Montel, Valérie, Delhaye, Stéphane, Thorel, Quentin, Beauchamp, Justine, Hebras, Aurore, Gimenez, Marion, Couvelaere, Marie, Zecchin, Mathilde, Ferri, Lise, Prevarskaya, Natalia, Forand, Anne, Gentil, Christel, Ohana, Jessica, Piétri-Rouxel, France, Bastide, Bruno, Staels, Bart, Duez, Helene, Lancel, Steve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536258/
https://www.ncbi.nlm.nih.gov/pubmed/35917173
http://dx.doi.org/10.1172/jci.insight.153584
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author Boulinguiez, Alexis
Duhem, Christian
Mayeuf-Louchart, Alicia
Pourcet, Benoit
Sebti, Yasmine
Kondratska, Kateryna
Montel, Valérie
Delhaye, Stéphane
Thorel, Quentin
Beauchamp, Justine
Hebras, Aurore
Gimenez, Marion
Couvelaere, Marie
Zecchin, Mathilde
Ferri, Lise
Prevarskaya, Natalia
Forand, Anne
Gentil, Christel
Ohana, Jessica
Piétri-Rouxel, France
Bastide, Bruno
Staels, Bart
Duez, Helene
Lancel, Steve
author_facet Boulinguiez, Alexis
Duhem, Christian
Mayeuf-Louchart, Alicia
Pourcet, Benoit
Sebti, Yasmine
Kondratska, Kateryna
Montel, Valérie
Delhaye, Stéphane
Thorel, Quentin
Beauchamp, Justine
Hebras, Aurore
Gimenez, Marion
Couvelaere, Marie
Zecchin, Mathilde
Ferri, Lise
Prevarskaya, Natalia
Forand, Anne
Gentil, Christel
Ohana, Jessica
Piétri-Rouxel, France
Bastide, Bruno
Staels, Bart
Duez, Helene
Lancel, Steve
author_sort Boulinguiez, Alexis
collection PubMed
description The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions, such as myopathies. Here, we investigated whether the nuclear receptor subfamily 1 group D member (NR1D1, also called REV-ERBα) regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that NR1D1 deficiency in mice impaired sarco/endoplasmic reticulum calcium ATPase–dependent (SERCA-dependent) SR calcium uptake. NR1D1 acts on calcium homeostasis by repressing the SERCA inhibitor myoregulin through direct binding to its promoter. Restoration of myoregulin counteracted the effects of NR1D1 overexpression on SR calcium content. Interestingly, myoblasts from patients with Duchenne muscular dystrophy displayed lower NR1D1 expression, whereas pharmacological NR1D1 activation ameliorated SR calcium homeostasis and improved muscle structure and function in dystrophic mdx/Utr(+/–) mice. Our findings demonstrate that NR1D1 regulates muscle SR calcium homeostasis, pointing to its therapeutic potential for mitigating myopathy.
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spelling pubmed-95362582022-10-07 NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression Boulinguiez, Alexis Duhem, Christian Mayeuf-Louchart, Alicia Pourcet, Benoit Sebti, Yasmine Kondratska, Kateryna Montel, Valérie Delhaye, Stéphane Thorel, Quentin Beauchamp, Justine Hebras, Aurore Gimenez, Marion Couvelaere, Marie Zecchin, Mathilde Ferri, Lise Prevarskaya, Natalia Forand, Anne Gentil, Christel Ohana, Jessica Piétri-Rouxel, France Bastide, Bruno Staels, Bart Duez, Helene Lancel, Steve JCI Insight Research Article The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions, such as myopathies. Here, we investigated whether the nuclear receptor subfamily 1 group D member (NR1D1, also called REV-ERBα) regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that NR1D1 deficiency in mice impaired sarco/endoplasmic reticulum calcium ATPase–dependent (SERCA-dependent) SR calcium uptake. NR1D1 acts on calcium homeostasis by repressing the SERCA inhibitor myoregulin through direct binding to its promoter. Restoration of myoregulin counteracted the effects of NR1D1 overexpression on SR calcium content. Interestingly, myoblasts from patients with Duchenne muscular dystrophy displayed lower NR1D1 expression, whereas pharmacological NR1D1 activation ameliorated SR calcium homeostasis and improved muscle structure and function in dystrophic mdx/Utr(+/–) mice. Our findings demonstrate that NR1D1 regulates muscle SR calcium homeostasis, pointing to its therapeutic potential for mitigating myopathy. American Society for Clinical Investigation 2022-09-08 /pmc/articles/PMC9536258/ /pubmed/35917173 http://dx.doi.org/10.1172/jci.insight.153584 Text en © 2022 Boulinguiez et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Boulinguiez, Alexis
Duhem, Christian
Mayeuf-Louchart, Alicia
Pourcet, Benoit
Sebti, Yasmine
Kondratska, Kateryna
Montel, Valérie
Delhaye, Stéphane
Thorel, Quentin
Beauchamp, Justine
Hebras, Aurore
Gimenez, Marion
Couvelaere, Marie
Zecchin, Mathilde
Ferri, Lise
Prevarskaya, Natalia
Forand, Anne
Gentil, Christel
Ohana, Jessica
Piétri-Rouxel, France
Bastide, Bruno
Staels, Bart
Duez, Helene
Lancel, Steve
NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression
title NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression
title_full NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression
title_fullStr NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression
title_full_unstemmed NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression
title_short NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression
title_sort nr1d1 controls skeletal muscle calcium homeostasis through myoregulin repression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536258/
https://www.ncbi.nlm.nih.gov/pubmed/35917173
http://dx.doi.org/10.1172/jci.insight.153584
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