An embryonic CaVß1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse.
Sci Transl Med
; 11(517)2019 11 06.
Article
em En
| MEDLINE
| ID: mdl-31694926
ABSTRACT
Deciphering the mechanisms that govern skeletal muscle plasticity is essential to understand its pathophysiological processes, including age-related sarcopenia. The voltage-gated calcium channel CaV1.1 has a central role in excitation-contraction coupling (ECC), raising the possibility that it may also initiate the adaptive response to changes during muscle activity. Here, we revealed the existence of a gene transcription switch of the CaV1.1 ß subunit (CaVß1) that is dependent on the innervation state of the muscle in mice. In a mouse model of sciatic denervation, we showed increased expression of an embryonic isoform of the subunit that we called CaVß1E. CaVß1E boosts downstream growth differentiation factor 5 (GDF5) signaling to counteract muscle loss after denervation in mice. We further reported that aged mouse muscle expressed lower quantity of CaVß1E compared with young muscle, displaying an altered GDF5-dependent response to denervation. Conversely, CaVß1E overexpression improved mass wasting in aging muscle in mice by increasing GDF5 expression. We also identified the human CaVß1E analogous and show a correlation between CaVß1E expression in human muscles and age-related muscle mass decline. These results suggest that strategies targeting CaVß1E or GDF5 might be effective in reducing muscle mass loss in aging.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Transdução de Sinais
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Canais de Cálcio Tipo L
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Embrião de Mamíferos
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Fator 5 de Diferenciação de Crescimento
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Músculos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Sci Transl Med
Ano de publicação:
2019
Tipo de documento:
Article