Copper promotes sheep pancreatic duct organoid growth by activation of an antioxidant protein 1-dependent MEK-ERK pathway.
Am J Physiol Cell Physiol
; 318(4): C806-C816, 2020 04 01.
Article
en En
| MEDLINE
| ID: mdl-32130071
ABSTRACT
Proper amounts of copper supplemented in livestock feed improve the physical growth and traits of farm animals. The pancreas is an important organ with both exocrine and endocrine portions. To investigate the role and mechanism of copper in the sheep pancreas, we first established sheep pancreatic duct organoids (sPDOs). We found that an appropriate amount of copper benefited the formation and growth of sPDOs, whereas excess or deficient copper damaged sPDOs. We found that the proliferation-stimulating effect of copper was related to the copper chaperone antioxidant protein 1 (ATOX1)-dependent activation of MEK-ERK1/2 signaling. Atox1 knockdown suppressed the cell proliferation of sPDOs, even in the presence of the MEK activator. These results indicate that moderate concentrations of copper promote sPDO growth through ATOX1-regulated cell proliferation by activation of MEK-ERK. Moreover, our study indicates that organoids may be a useful model to study organ growth mechanisms in livestock.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Conductos Pancreáticos
/
Transducción de Señal
/
Cobre
/
Sistema de Señalización de MAP Quinasas
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article