p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition
Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin,...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.677746/full |
| _version_ | 1818613556603518976 |
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| author | Caroline Barbé Audrey Loumaye Pascale Lause Olli Ritvos Jean-Paul Thissen |
| author_facet | Caroline Barbé Audrey Loumaye Pascale Lause Olli Ritvos Jean-Paul Thissen |
| author_sort | Caroline Barbé |
| collection | DOAJ |
| description | Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development. Indeed, its inhibition induces an extensive skeletal muscle hypertrophy requiring the activation of Smad 1/5/8 and the Insulin/IGF-I signaling pathway, but whether other molecular mechanisms are involved in this process remains to be determined. Using transcriptomic data from various Myostatin inhibition models, we identified Pak1 as a potential mediator of Myostatin action on skeletal muscle mass. Our results show that muscle PAK1 levels are systematically increased in response to Myostatin inhibition, parallel to skeletal muscle mass, regardless of the Myostatin inhibition model. Using Pak1 knockout mice, we investigated the role of Pak1 in the skeletal muscle hypertrophy induced by different approaches of Myostatin inhibition. Our findings show that Pak1 deletion does not impede the skeletal muscle hypertrophy magnitude in response to Myostatin inhibition. Therefore, Pak1 is permissive for the skeletal muscle mass increase caused by Myostatin inhibition. |
| first_indexed | 2024-12-16T16:04:00Z |
| format | Article |
| id | doaj.art-fa014cd56d9e414fb53bb8b6823c08f4 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-16T16:04:00Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-fa014cd56d9e414fb53bb8b6823c08f42022-12-21T22:25:25ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.677746677746p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin InhibitionCaroline Barbé0Audrey Loumaye1Pascale Lause2Olli Ritvos3Jean-Paul Thissen4Pole of Endocrinology, Diabetes and Nutrition, Institute of Clinical and Experimental Research, Catholic University of Louvain, Brussels, BelgiumPole of Endocrinology, Diabetes and Nutrition, Institute of Clinical and Experimental Research, Catholic University of Louvain, Brussels, BelgiumPole of Endocrinology, Diabetes and Nutrition, Institute of Clinical and Experimental Research, Catholic University of Louvain, Brussels, BelgiumDepartment of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, FinlandPole of Endocrinology, Diabetes and Nutrition, Institute of Clinical and Experimental Research, Catholic University of Louvain, Brussels, BelgiumSkeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development. Indeed, its inhibition induces an extensive skeletal muscle hypertrophy requiring the activation of Smad 1/5/8 and the Insulin/IGF-I signaling pathway, but whether other molecular mechanisms are involved in this process remains to be determined. Using transcriptomic data from various Myostatin inhibition models, we identified Pak1 as a potential mediator of Myostatin action on skeletal muscle mass. Our results show that muscle PAK1 levels are systematically increased in response to Myostatin inhibition, parallel to skeletal muscle mass, regardless of the Myostatin inhibition model. Using Pak1 knockout mice, we investigated the role of Pak1 in the skeletal muscle hypertrophy induced by different approaches of Myostatin inhibition. Our findings show that Pak1 deletion does not impede the skeletal muscle hypertrophy magnitude in response to Myostatin inhibition. Therefore, Pak1 is permissive for the skeletal muscle mass increase caused by Myostatin inhibition.https://www.frontiersin.org/articles/10.3389/fphys.2021.677746/fullmyostatinfollistatinsActRIIBPAK1skeletal muscle hypertrophy |
| spellingShingle | Caroline Barbé Audrey Loumaye Pascale Lause Olli Ritvos Jean-Paul Thissen p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition Frontiers in Physiology myostatin follistatin sActRIIB PAK1 skeletal muscle hypertrophy |
| title | p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition |
| title_full | p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition |
| title_fullStr | p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition |
| title_full_unstemmed | p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition |
| title_short | p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition |
| title_sort | p21 activated kinase 1 is permissive for the skeletal muscle hypertrophy induced by myostatin inhibition |
| topic | myostatin follistatin sActRIIB PAK1 skeletal muscle hypertrophy |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.677746/full |
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