Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration
In skeletal muscle, transforming growth factor-β (TGF-β) family growth factors, TGF-β1 and myostatin, are involved in atrophy and muscle wasting disorders. Simultaneous interference with their signalling pathways may improve muscle function; however, little is known about their individual and combin...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/77610 |
| _version_ | 1818026533280808960 |
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| author | Michèle MG Hillege Andi Shi Ricardo A Galli Gang Wu Philippe Bertolino Willem MH Hoogaars Richard T Jaspers |
| author_facet | Michèle MG Hillege Andi Shi Ricardo A Galli Gang Wu Philippe Bertolino Willem MH Hoogaars Richard T Jaspers |
| author_sort | Michèle MG Hillege |
| collection | DOAJ |
| description | In skeletal muscle, transforming growth factor-β (TGF-β) family growth factors, TGF-β1 and myostatin, are involved in atrophy and muscle wasting disorders. Simultaneous interference with their signalling pathways may improve muscle function; however, little is known about their individual and combined receptor signalling. Here, we show that inhibition of TGF-β signalling by simultaneous muscle-specific knockout of TGF-β type I receptors Tgfbr1 and Acvr1b in mice, induces substantial hypertrophy, while such effect does not occur by single receptor knockout. Hypertrophy is induced by increased phosphorylation of Akt and p70S6K and reduced E3 ligases expression, while myonuclear number remains unaltered. Combined knockout of both TGF-β type I receptors increases the number of satellite cells, macrophages and improves regeneration post cardiotoxin-induced injury by stimulating myogenic differentiation. Extra cellular matrix gene expression is exclusively elevated in muscle with combined receptor knockout. Tgfbr1 and Acvr1b are synergistically involved in regulation of myofibre size, regeneration, and collagen deposition. |
| first_indexed | 2024-12-10T04:33:31Z |
| format | Article |
| id | doaj.art-e3a9868a263f44ff871063dfe9851fd7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:33:31Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e3a9868a263f44ff871063dfe9851fd72022-12-22T02:02:05ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.77610Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regenerationMichèle MG Hillege0https://orcid.org/0000-0001-7857-8994Andi Shi1https://orcid.org/0000-0001-6364-5437Ricardo A Galli2Gang Wu3Philippe Bertolino4https://orcid.org/0000-0001-8064-8269Willem MH Hoogaars5Richard T Jaspers6https://orcid.org/0000-0002-6951-0952Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands; Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands; Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, NetherlandsDepartment of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, NetherlandsCentre de Recherche en Cancérologie de Lyon, UMR INSERM U1052/CNRS 5286, Université de Lyon, Centre Léon Bérard, Lyon, FranceLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands; Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands; Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, ChinaIn skeletal muscle, transforming growth factor-β (TGF-β) family growth factors, TGF-β1 and myostatin, are involved in atrophy and muscle wasting disorders. Simultaneous interference with their signalling pathways may improve muscle function; however, little is known about their individual and combined receptor signalling. Here, we show that inhibition of TGF-β signalling by simultaneous muscle-specific knockout of TGF-β type I receptors Tgfbr1 and Acvr1b in mice, induces substantial hypertrophy, while such effect does not occur by single receptor knockout. Hypertrophy is induced by increased phosphorylation of Akt and p70S6K and reduced E3 ligases expression, while myonuclear number remains unaltered. Combined knockout of both TGF-β type I receptors increases the number of satellite cells, macrophages and improves regeneration post cardiotoxin-induced injury by stimulating myogenic differentiation. Extra cellular matrix gene expression is exclusively elevated in muscle with combined receptor knockout. Tgfbr1 and Acvr1b are synergistically involved in regulation of myofibre size, regeneration, and collagen deposition.https://elifesciences.org/articles/77610TGF-βmyostatintype I receptorhypertrophyinjuryskeletal muscle |
| spellingShingle | Michèle MG Hillege Andi Shi Ricardo A Galli Gang Wu Philippe Bertolino Willem MH Hoogaars Richard T Jaspers Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration eLife TGF-β myostatin type I receptor hypertrophy injury skeletal muscle |
| title | Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration |
| title_full | Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration |
| title_fullStr | Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration |
| title_full_unstemmed | Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration |
| title_short | Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration |
| title_sort | lack of tgfbr1 and acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration |
| topic | TGF-β myostatin type I receptor hypertrophy injury skeletal muscle |
| url | https://elifesciences.org/articles/77610 |
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