Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling.
J Lipid Res
; 46(3): 458-68, 2005 Mar.
Article
em En
| MEDLINE
| ID: mdl-15604525
ABSTRACT
Three genes, fibrinogen-alpha (FBGalpha), -beta, and -gamma, encode proteins that make up the mature FBG protein complex. This complex is secreted from the liver and plays a key role in coagulation in response to vascular disruption. We identified all three FBG genes in a screen designed to isolate genes that are regulated by the farnesoid X receptor (FXR; NR1H4). Treatment of human hepatoma cells with either naturally occurring or synthetic [3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole] FXR ligands resulted in the induction of transcripts for all three genes. The induction of FBGbeta mRNA in response to activated FXR appears to be a primary transcriptional response, as it is blocked by actinomycin D but not by cycloheximide. Four FXR isoforms were recently identified that differ either at their N termini and/or by the presence of four amino acids in the hinge region. Interestingly, the activities of the human FBGbeta promoter-reporter constructs were highly induced by FXR isoforms that lack the four amino acid insert. The observation that all three FBG subunits are induced by specific FXR isoforms, in response to FXR ligands, suggests that bile acids and FXR modulate fibrinolytic activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Fibrinogênio
/
Ácidos e Sais Biliares
/
Transdução de Sinais
/
Regulação da Expressão Gênica
/
Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos