Osteopontin is linked with AKT, FoxO1, and myostatin in skeletal muscle cells.
Muscle Nerve
; 56(6): 1119-1127, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28745831
ABSTRACT
INTRODUCTION:
Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN).METHODS:
Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in-vitro studies were employed in myogenic cells and the mdx mouse treated with recombinant mouse (rm) or human (Hu) OPN protein.RESULTS:
OPN was increased and MSTN was decreased and levels correlated inversely in GRMD hypertrophied muscle. RM-OPN treatment led to induced AKT1 and FoxO1 phosphorylation, microRNA-486 modulation, and decreased MSTN. An AKT1 inhibitor blocked these effects, whereas an RGD-mutant OPN protein and an RGDS blocking peptide showed similar effects to the AKT inhibitor. RMOPN induced myotube hypertrophy and minimal Feret diameter in mdx muscle.DISCUSSION:
OPN may interact with AKT1/MSTN/FoxO1 to modify normal and dystrophic muscle. Muscle Nerve 56 1119-1127, 2017.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fibras Musculares Esqueléticas
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Mioblastos
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Proteínas Proto-Oncogênicas c-akt
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Osteopontina
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Miostatina
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Proteína Forkhead Box O1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Muscle Nerve
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos