Efficient adult skeletal muscle regeneration in mice deficient in p38beta, p38gamma and p38delta MAP kinases.
Adult skeletal muscle is a very stable tissue containing a small population of myofiber-associated quiescent satellite cells compared with late embryonic/neonatal skeletal muscle, which contains highly proliferating myoblasts and small actively growing myofibers, suggesting that specific regulatory pathways may control myogenesis at distinct developmental stages. The p38 MAPK signaling pathway is central for myogenesis, based on studies using immortalized and neonatal primary myoblasts in vitro. However, the contribution of this pathway to adult myogenesis has never been investigated. Four p38 isoforms (p38alpha, p38beta, p38gamma and p38delta) exist in mammalian cells, being p38alpha and p38gamma the most abundantly expressed isoforms in adult skeletal muscle. Given the embryonic/neonatal lethality of p38alpha-deficient mice, here we investigate the relative contribution of p38beta, p38gamma and p38delta to adult myogenesis. Regeneration and myofiber growth of adult muscle proceeds with similar efficiency in mice lacking p38beta, p38gamma and p38delta as in wild-type control mice. In agreement with this, there is no difference in adult primary myoblasts behavior in vitro among the different genotypes. Importantly, the pattern of p38 activation (ascribed to p38alpha) remains unperturbed during satellite cell-mediated myogenesis in vitro and adult muscle regeneration in wild type and p38beta-, p38gamma- and p38delta-deficient mice, rendering p38alpha as the essential p38 isoform sustaining adult myogenesis. This study constitutes the first analysis addressing the functionality of p38beta, p38gamma and p38delta in satellite cell-dependent adult muscle regeneration and growth.
Ruiz-Bonilla
Vanessa
V
Center for Genomic Regulation, Pompeu Fabra University, Program on Differentiation and Cancer and Biomedicine Research Center on Neurodegenerative Diseases, Barcelona, Spain.
Perdiguero
Eusebio
E
Gresh
Lionel
L
Serrano
Antonio L
AL
Zamora
Mònica
M
Sousa-Victor
Pedro
P
Jardí
Mercè
M
Wagner
Erwin F
EF
Muñoz-Cánoves
Pura
P
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002459:Cell Fusion; D049109:Cell Proliferation; D002478:Cells, Cultured; D051379:Mice; D048290:Mitogen-Activated Protein Kinase 11 / Q000172:deficiency; D048291:Mitogen-Activated Protein Kinase 12 / Q000172:deficiency; D048292:Mitogen-Activated Protein Kinase 13 / Q000172:deficiency; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000201:enzymology; D010641:Phenotype; D012038:Regeneration; D048051:p38 Mitogen-Activated Protein Kinases / Q000172:deficiency*
D015415:Biomarkers; D048291:Mitogen-Activated Protein Kinase 12; D048292:Mitogen-Activated Protein Kinase 13; D048290:Mitogen-Activated Protein Kinase 11; D048051:p38 Mitogen-Activated Protein Kinases