title: Nuclear receptors in acute and chronic cholestasis.
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.
  
  
  CONCLUSIONS
  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/β (REV-ERB α/β), 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.
authors.affiliation: INSERM UMR_S 938, Centre de Recherche Saint-Antoine, and Sorbonne Universités, UPMC Université Paris 06, Paris, France.
authors.forename: Ester
authors.initials: E
authors.lastname: Gonzalez-Sanchez
authors.forename: Delphine
authors.initials: D
authors.lastname: Firrincieli
authors.forename: Chantal
authors.initials: C
authors.lastname: Housset
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chignard
mesh_terms: D000208:Acute Disease; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism* / Q000628:therapy; D002908:Chronic Disease; D057906:Circadian Clocks; D004734:Energy Metabolism; D006801:Humans; D050356:Lipid Metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear