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Research article - Peer-reviewed, 2021

Concurrent BMP Signaling Maintenance and TGF-beta Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear

Cussonneau, Laura; Boyer, Christian; Brun, Charlotte; Deval, Christiane; Loizon, Emmanuelle; Meugnier, Emmanuelle; Gueret, Elise; Dubois, Emeric; Taillandier, Daniel; Polge, Cecile; Bechet, Daniel; Gauquelin-Koch, Guillemette; Evans, Alina L.; Arnemo, Jon M.; Swenson, Jon E.; Blanc, Stephane; Simon, Chantal; Lefai, Etienne; Bertile, Fabrice; Combaret, Lydie

Abstract

Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-beta and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-beta- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-beta/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-beta inhibiting therapies already targeted to prevent muscle atrophy.

Keywords

brown bear hibernation; mouse unloading; muscle atrophy; physical inactivity; RNA sequencing; TGF-beta/BMP signaling

Published in

Cells
2021, volume: 10, number: 8, article number: 1873
Publisher: MDPI

Authors' information

Cussonneau, Laura
Universite Clermont Auvergne (UCA)
Boyer, Christian
Universite Clermont Auvergne (UCA)
Brun, Charlotte
Universites de Strasbourg Etablissements Associes
Deval, Christiane
Universite Clermont Auvergne (UCA)
Loizon, Emmanuelle
Institut National de la Sante et de la Recherche Medicale (Inserm)
Meugnier, Emmanuelle
Institut National de la Sante et de la Recherche Medicale (Inserm)
Gueret, Elise
Universite de Montpellier
Dubois, Emeric
Universite de Montpellier
Taillandier, Daniel
Universite Clermont Auvergne (UCA)
Polge, Cecile
Universite Clermont Auvergne (UCA)
Bechet, Daniel
Universite Clermont Auvergne (UCA)
Gauquelin-Koch, Guillemette
Centre national d'études spatiales (CNES)
Evans, Alina L.
Inland Norway University of Applied Sciences
Inland Norway University of Applied Sciences
Swedish University of Agricultural Sciences, Department of Wildlife, Fish and Environmental Studies
Swenson, Jon E.
Norwegian University of Life Sciences
Blanc, Stephane
Universites de Strasbourg Etablissements Associes
Simon, Chantal
Institut National de la Sante et de la Recherche Medicale (Inserm)
Lefai, Etienne
Universite Clermont Auvergne (UCA)
Bertile, Fabrice
Universites de Strasbourg Etablissements Associes

UKÄ Subject classification

Zoology

Publication Identifiers

DOI: https://doi.org/10.3390/cells10081873

URI (permanent link to this page)

https://res.slu.se/id/publ/113522