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
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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