Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice

摘要: Abstract Background & Aims: Cholestasis induces changes in hepatic adenosine triphosphate-binding cassette (ABC) transporter expression. We aimed to investigate the role of nuclear bile acid receptor (farnesoid X [FXR]) mediating ABC expression and determining liver injury. Methods: Hepatic (multidrug resistance-associated proteins [Mrp] 2–4 salt export pump [Bsep]) localization were studied common duct-ligated (CBDL) FXR knockout (FXR −/− ), wild-type +/+ sham-operated mice. Serum alanine aminotransferase, alkaline phosphatase, bilirubin levels, composition, histology investigated. Cholangiomanometry duct morphometry performed. Results: CBDL induced Mrp 3 4 even more , whereas 2 remained unchanged. Bsep was maintained but undetectable . Alanine aminotransferase levels mortality rates did not differ between increased biliary pressure ductular proliferation infarcts had lower pressures, less proliferation, developed disseminated cell necroses. Conclusions: Overexpression mice is independent could play an important adaptive response cholestasis. Maintenance strictly depends on a critical determinant cholestatic phenotype. Lack suggests that development related acid-dependent flow pressure. This information relevant for potential use modulators treatment diseases.