Nuclear receptors in acute and chronic cholestasis.
Dig Dis
; 33(3): 357-66, 2015.
Article
en En
| MEDLINE
| ID: mdl-26045270
ABSTRACT
BACKGROUND:
Nuclear receptors (NRs) form a family of 48 members. NRs control hepatic processes such as bile acid homeostasis, lipid metabolism and mechanisms involved in fibrosis and inflammation. Due to their central role in the regulation of hepatoprotective mechanisms, NRs are promising therapeutic targets in cholestatic disorders. KEY MESSAGES NRs can be classified into five different physiological clusters. NRs from the 'bile acids and xenobiotic metabolism' and from the 'lipid metabolism and energy homeostasis' clusters are strongly expressed in the liver. Furthermore, NRs from these clusters, such as farnesoid X receptor α (FXRα), pregnane X receptor (PXR) and peroxisome proliferator-activated receptors (PPARs), have been associated with the pathogenesis and the progression of cholestasis. The latter observation is also true for vitamin D receptor (VDR), which is barely detectable in the whole liver, but has been linked to cholestatic diseases. Involvement of VDR in cholestasis is ascribed to a strong expression in nonparenchymal liver cells, such as biliary epithelial cells, Kupffer cells and hepatic stellate cells. Likewise, NRs from other physiological clusters with low hepatic expression, such as estrogen receptor α (ERα) or reverse-Erb α/ß (REV-ERB α/ß), may also control pathophysiological processes in cholestasis.CONCLUSIONS:
In this review, we will describe the impact of individual NRs on cholestasis. We will then discuss the potential role of these transcription factors as therapeutic targets.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácidos y Sales Biliares
/
Colestasis
/
Receptores Citoplasmáticos y Nucleares
/
Metabolismo Energético
/
Metabolismo de los Lípidos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Dig Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia