Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis.
Genes Dev
; 17(13): 1581-91, 2003 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-12815072
ABSTRACT
The nuclear bile acid receptor FXR has been proposed to play a central role in the feedback repression of the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the first and rate-limiting step in the biosynthesis of bile acids. We demonstrate that FXR directly regulates expression of fibroblast growth factor-19 (FGF-19), a secreted growth factor that signals through the FGFR4 cell-surface receptor tyrosine kinase. In turn, FGF-19 strongly suppresses expression of CYP7A1 in primary cultures of human hepatocytes and mouse liver through a c-Jun N-terminal kinase (JNK)-dependent pathway. This signaling cascade defines a novel mechanism for feedback repression of bile acid biosynthesis and underscores the vital role of FXR in the regulation of multiple pathways of cholesterol catabolism in the liver.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Ácidos e Sais Biliares
/
Colesterol 7-alfa-Hidroxilase
/
Transdução de Sinais
/
Hepatócitos
/
Proteínas de Ligação a DNA
/
Fatores de Crescimento de Fibroblastos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Genes Dev
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos