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Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice / 生理学报
Acta Physiologica Sinica ; (6): 795-804, 2021.
Artículo en Inglés | WPRIM | ID: wpr-921282
ABSTRACT
Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Coagulación Sanguínea / Antitrombina III / Receptores Citoplasmáticos y Nucleares / Ratones Noqueados / Hepatocitos / Hígado / Ratones Endogámicos C57BL Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Inglés Revista: Acta Physiologica Sinica Año: 2021 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Coagulación Sanguínea / Antitrombina III / Receptores Citoplasmáticos y Nucleares / Ratones Noqueados / Hepatocitos / Hígado / Ratones Endogámicos C57BL Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Inglés Revista: Acta Physiologica Sinica Año: 2021 Tipo del documento: Artículo