Myostatin regulates the fibrogenic phenotype of hepatic stellate cells via c-jun N-terminal kinase activation.
Dig Liver Dis
; 51(10): 1400-1408, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31005555
ABSTRACT
BACKGROUND & AIMS:
Myostatin is mainly expressed in skeletal muscle, where it negatively regulates trophism. This myokine is implicated in the pathophysiology of nonalcoholic steatohepatitis, an emerging cause of liver fibrosis. In this study we explored the effects of myostatin on the biology of hepatic stellate cells.METHODS:
The effects of myostatin were assessed both in LX-2 and in human primary stellate cells. Cell migration was determined in Boyden chambers. Activation of intracellular pathways was evaluated by Western blotting. Procollagen type 1 secretion was measured by enzyme immunoassay. The role of c-Jun N-terminal kinase was assessed by pharmacologic and genetic inhibition.RESULTS:
Activin receptor-2B was up-regulated in livers of mice with experimental fibrosis, and detectable in human stellate cells. Serum myostatin levels increased in a model of acute liver injury. Myostatin reduced HSC proliferation, induced cell migration, and increased expression of procollagen type1, tissue inhibitor of metalloproteinase-1, and transforming growth factor-ß1. Myostatin activated different signaling pathways, including c-Jun N-terminal kinase and Smad3. Genetic and/or pharmacologic inhibition of c-Jun N-terminal kinase activity significantly reduced cell migration and procollagen secretion in response to myostatin.CONCLUSIONS:
Activation of activin receptor-2B by myostatin modulates the fibrogenic phenotype of human stellate cells, indicating that a myokine may be implicated in the pathogenesis of hepatic fibrosis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Activinas Tipo II
/
Proteínas Quinases JNK Ativadas por Mitógeno
/
Células Estreladas do Fígado
/
Miostatina
/
Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Dig Liver Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália