Myofibroblast induces hepatocyte-to-ductal metaplasia via laminin-Évß6 integrin in liver fibrosis.
Cell Death Dis
; 11(3): 199, 2020 03 23.
Article
en En
| MEDLINE
| ID: mdl-32251270
ABSTRACT
Hepatocytes undergo the metaplasia into ductal biliary epithelial cells (BECs) in response to chronic injury, and subsequently contribute to liver regeneration. The mechanism underlying hepatocyte-to-ductal metaplasia has not been explored until now. In mouse models of liver fibrosis, a florid BEC response was observed in fibrotic liver, and the depletion of myofibroblasts attenuated BEC expansion remarkably. Then, in hepatocyte fate-tracing mouse model, we demonstrated the conversion of mature hepatocytes into ductal BECs in fibrotic liver, and the depletion of myofibroblasts diminished the hepatocyte-to-ductal metaplasia. Finally, the mechanism underlying the metaplasia was investigated. Myofibroblasts secreted laminin-rich extracellular matrix, and then laminin induced hepatocyte-to-ductal metaplasia through Évß6 integrin. Therefore, our results demonstrated myofibroblasts induce the conversion of mature hepatocytes into ductal BECs through laminin-Évß6 integrin, which reveals that the strategy improve regeneration in fibrotic liver through the modification of specific microenvironment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Integrinas
/
Laminina
/
Miofibroblastos
/
Cirrosis Hepática
/
Antígenos de Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2020
Tipo del documento:
Article
País de afiliación:
China