Nitric Oxide Sustains Long-Term Skeletal Muscle Regeneration by Regulating Fate of Satellite Cells Via Signaling Pathways Requiring Vangl2 and Cyclic GMP
Autor: | Roberta Buono, Clara Sciorati, Maria Teresa Bassi, Chiara Vantaggiato, Silvia Brunelli, Emanuele Azzoni, Viviana Pisa, Emilio Clementi |
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Přispěvatelé: | Buono, R, Vantaggiato, C, Pisa, V, Azzoni, E, Bassi, M, Brunelli, S, Sciorati, C, Clementi, E |
Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
medicine.medical_specialty
Mice 129 Strain Satellite Cells Skeletal Muscle Skeletal muscle Nerve Tissue Proteins Signal transduction Biology Muscle Development Nitric Oxide Regenerative Medicine Muscular Dystrophies Nitric oxide Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Regeneration Nitric Oxide Donors Muscular dystrophy Muscle Skeletal Cyclic GMP Cells Cultured Cell Proliferation 030304 developmental biology 0303 health sciences Myogenesis Regeneration (biology) Wnt signaling pathway Cell Differentiation Cell Biology medicine.disease Cell biology medicine.anatomical_structure Endocrinology Gene Expression Regulation chemistry Molsidomine Self-renewal Molecular Medicine Female Stem cell 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | STEM CELLS; Vol 30 STEM CELLS Stem Cells (Dayton, Ohio) |
ISSN: | 1066-5099 |
DOI: | 10.1002/stem.783 |
Popis: | Satellite cells are myogenic precursors that proliferate, activate, and differentiate on muscle injury to sustain the regenerative capacity of adult skeletal muscle; in this process, they self-renew through the return to quiescence of the cycling progeny. This mechanism, while efficient in physiological conditions does not prevent exhaustion of satellite cells in pathologies such as muscular dystrophy where numerous rounds of damage occur. Here, we describe a key role of nitric oxide, an important signaling molecule in adult skeletal muscle, on satellite cells maintenance, studied ex vivo on isolated myofibers and in vivo using the α-sarcoglycan null mouse model of dystrophy and a cardiotoxin-induced model of repetitive damage. Nitric oxide stimulated satellite cells proliferation in a pathway dependent on cGMP generation. Furthermore, it increased the number of Pax7+/Myf5− cells in a cGMP-independent pathway requiring enhanced expression of Vangl2, a member of the planar cell polarity pathway involved in the Wnt noncanonical pathway. The enhanced self-renewal ability of satellite cells induced by nitric oxide is sufficient to delay the reduction of the satellite cell pool during repetitive acute and chronic damages, favoring muscle regeneration; in the α-sarcoglycan null dystrophic mouse, it also slowed disease progression persistently. These results identify nitric oxide as a key messenger in satellite cells maintenance, expand the significance of the Vangl2-dependent Wnt noncanonical pathway in myogenesis, and indicate novel strategies to optimize nitric oxide-based therapies for muscular dystrophy. Disclosure of potential conflicts of interest is found at the end of this article. |
Databáze: | OpenAIRE |
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