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1.
Nat Commun ; 8: 15201, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28541289

RESUMO

A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli.


Assuntos
MicroRNAs/metabolismo , Atrofia Muscular/classificação , Atrofia Muscular/genética , Animais , Sequência de Bases , Linhagem Celular , Regulação da Expressão Gênica , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Atrofia Muscular/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Regulação para Cima/genética , Fator de Transcrição YY1/metabolismo
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