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

Cussonneau, Laura and Boyer, Christian and Brun, Charlotte and Deval, Christiane and Loizon, Emmanuelle and Meugnier, Emmanuelle and Gueret, Elise and Dubois, Emeric and Taillandier, Daniel and Polge, Cecile and Bechet, Daniel and Gauquelin-Koch, Guillemette and Evans, Alina L. and Arnemo, Jon and Swenson, Jon E. and Blanc, Stephane and Simon, Chantal and Lefai, Etienne and Bertile, Fabrice and Combaret, Lydie (2021). Concurrent BMP Signaling Maintenance and TGF-beta Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear. Cells. 10 , 1873
[Research article]

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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.

Authors/Creators:Cussonneau, Laura and Boyer, Christian and Brun, Charlotte and Deval, Christiane and Loizon, Emmanuelle and Meugnier, Emmanuelle and Gueret, Elise and Dubois, Emeric and Taillandier, Daniel and Polge, Cecile and Bechet, Daniel and Gauquelin-Koch, Guillemette and Evans, Alina L. and Arnemo, Jon and Swenson, Jon E. and Blanc, Stephane and Simon, Chantal and Lefai, Etienne and Bertile, Fabrice and Combaret, Lydie
Title:Concurrent BMP Signaling Maintenance and TGF-beta Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear
Series Name/Journal:Cells
Year of publishing :2021
Volume:10
Article number:1873
Number of Pages:22
Publisher:MDPI
ISSN:2073-4409
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Zoology
Keywords:brown bear hibernation, mouse unloading, muscle atrophy, physical inactivity, RNA sequencing, TGF-beta/BMP signaling
URN:NBN:urn:nbn:se:slu:epsilon-p-113522
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-113522
Additional ID:
Type of IDID
DOI10.3390/cells10081873
Web of Science (WoS)000688955200001
ID Code:25306
Faculty:S - Faculty of Forest Sciences
Department:(S) > Dept. of Wildlife, Fish and Environmental Studies
Deposited By: SLUpub Connector
Deposited On:10 Sep 2021 16:25
Metadata Last Modified:10 Sep 2021 16:31

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