Arnemo, Jon
- Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences
- Inland Norway University of Applied Sciences
Research article2021Peer reviewedOpen access
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
SLU Authors
UKÄ Subject classification
Zoology
Publication identifier
- DOI: https://doi.org/10.3390/cells10081873
Permanent link to this page (URI)
https://res.slu.se/id/publ/113522