p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition
| Autor: | Olli Ritvos, Jean-Paul Thissen, Audrey Loumaye, Pascale Lause, Caroline Barbé |
|---|---|
| Přispěvatelé: | UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Department of Physiology, Growth factor physiology, Faculty of Medicine, University of Helsinki |
| Rok vydání: | 2021 |
| Předmět: |
EXPRESSION
0301 basic medicine Physiology SMAD Myostatin ATROPHY PATHWAY skeletal muscle hypertrophy 03 medical and health sciences 0302 clinical medicine PAK1 Physiology (medical) KINASE follistatin medicine DYSTROPHIN QP1-981 Original Research IIB RECEPTOR biology Chemistry 1184 Genetics developmental biology physiology Skeletal muscle musculoskeletal system Cell biology MICE 030104 developmental biology medicine.anatomical_structure myostatin Knockout mouse PROTEIN-SYNTHESIS biology.protein GROWTH 3111 Biomedicine Signal transduction Dystrophin sActRIIB 030217 neurology & neurosurgery Follistatin |
| Zdroj: | Frontiers in physiology, Vol. 12, p. 677746 [1-13] (2021) Frontiers in Physiology, Vol 12 (2021) Frontiers in Physiology |
| ISSN: | 1664-042X |
| Popis: | 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 identifiedPak1as 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. UsingPak1knockout mice, we investigated the role ofPak1in the skeletal muscle hypertrophy induced by different approaches of Myostatin inhibition. Our findings show thatPak1deletion does not impede the skeletal muscle hypertrophy magnitude in response to Myostatin inhibition. Therefore,Pak1is permissive for the skeletal muscle mass increase caused by Myostatin inhibition. |
| Databáze: | OpenAIRE |
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