Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear
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 atro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/8/1873 |
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| author | Laura Cussonneau Christian Boyer Charlotte Brun Christiane Deval Emmanuelle Loizon Emmanuelle Meugnier Elise Gueret Emeric Dubois Daniel Taillandier Cécile Polge Daniel Béchet Guillemette Gauquelin-Koch Alina L. Evans Jon M. Arnemo Jon E. Swenson Stéphane Blanc Chantal Simon Etienne Lefai Fabrice Bertile Lydie Combaret |
| author_facet | Laura Cussonneau Christian Boyer Charlotte Brun Christiane Deval Emmanuelle Loizon Emmanuelle Meugnier Elise Gueret Emeric Dubois Daniel Taillandier Cécile Polge Daniel Béchet Guillemette Gauquelin-Koch Alina L. Evans Jon M. Arnemo Jon E. Swenson Stéphane Blanc Chantal Simon Etienne Lefai Fabrice Bertile Lydie Combaret |
| author_sort | Laura Cussonneau |
| collection | DOAJ |
| description | 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)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- 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-β/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-β inhibiting therapies already targeted to prevent muscle atrophy. |
| first_indexed | 2024-03-10T08:55:33Z |
| format | Article |
| id | doaj.art-72fb005e5d134915a9cdabf9bcf78b9f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:33Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-72fb005e5d134915a9cdabf9bcf78b9f2023-11-22T07:08:33ZengMDPI AGCells2073-44092021-07-01108187310.3390/cells10081873Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating BearLaura Cussonneau0Christian Boyer1Charlotte Brun2Christiane Deval3Emmanuelle Loizon4Emmanuelle Meugnier5Elise Gueret6Emeric Dubois7Daniel Taillandier8Cécile Polge9Daniel Béchet10Guillemette Gauquelin-Koch11Alina L. Evans12Jon M. Arnemo13Jon E. Swenson14Stéphane Blanc15Chantal Simon16Etienne Lefai17Fabrice Bertile18Lydie Combaret19INRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceUniversité de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceCarMen Laboratory, INSERM 1060, INRAE 1397, University of Lyon, F-69600 Oullins, FranceCarMen Laboratory, INSERM 1060, INRAE 1397, University of Lyon, F-69600 Oullins, FranceInstitut de Génomique Fonctionnelle (IGF), University Montpellier, CNRS, INSERM, 34094 Montpellier, FranceInstitut de Génomique Fonctionnelle (IGF), University Montpellier, CNRS, INSERM, 34094 Montpellier, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceCentre National d’Etudes Spatiales, CNES, 75001 Paris, FranceDepartment of Forestry and Wildlife Management, Inland Norway University of Applied Sciences, Campus Evenstad, NO-2480 Koppang, NorwayDepartment of Forestry and Wildlife Management, Inland Norway University of Applied Sciences, Campus Evenstad, NO-2480 Koppang, NorwayFaculty of Environmental Sciences and Natural Resource Management, Norwegian University of Life Sciences, NO-1432 Ås, NorwayUniversité de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, FranceCarMen Laboratory, INSERM 1060, INRAE 1397, University of Lyon, F-69600 Oullins, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceUniversité de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, FranceINRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, FranceMuscle 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)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- 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-β/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-β inhibiting therapies already targeted to prevent muscle atrophy.https://www.mdpi.com/2073-4409/10/8/1873brown bear hibernationmouse unloadingmuscle atrophyphysical inactivityRNA sequencingTGF-β/BMP signaling |
| spellingShingle | Laura Cussonneau Christian Boyer Charlotte Brun Christiane Deval Emmanuelle Loizon Emmanuelle Meugnier Elise Gueret Emeric Dubois Daniel Taillandier Cécile Polge Daniel Béchet Guillemette Gauquelin-Koch Alina L. Evans Jon M. Arnemo Jon E. Swenson Stéphane Blanc Chantal Simon Etienne Lefai Fabrice Bertile Lydie Combaret Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear Cells brown bear hibernation mouse unloading muscle atrophy physical inactivity RNA sequencing TGF-β/BMP signaling |
| title | Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear |
| title_full | Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear |
| title_fullStr | Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear |
| title_full_unstemmed | Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear |
| title_short | Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear |
| title_sort | concurrent bmp signaling maintenance and tgf β signaling inhibition is a hallmark of natural resistance to muscle atrophy in the hibernating bear |
| topic | brown bear hibernation mouse unloading muscle atrophy physical inactivity RNA sequencing TGF-β/BMP signaling |
| url | https://www.mdpi.com/2073-4409/10/8/1873 |
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