ArticleJournal of lipid research2013
Mechanistic insights into isoform-dependent and species-specific regulation of bile salt export pump by farnesoid X receptor.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Baohuoside I inhibits FXR signaling pathway to interfere with bile acid homeostasis via targeting ER α degradation.Cell biology and toxicology · 2023Article
- The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity.International journal of molecular sciences · 2022Review
- Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism.Molecular and cellular endocrinology · 2022Review
- A minimal bile salt excretory pump promoter allows bile acid-driven physiological regulation of transgene expression from a gene therapy vector.Cell & bioscience · 2022Article
- Quantification of common and planar bile acids in tissues and cultured cells.Journal of lipid research · 2020Article
- AInternational journal of molecular sciences · 2020Article
- Metformin Disrupts Bile Acid Efflux by Repressing Bile Salt Export Pump Expression.Pharmaceutical research · 2020Article
- Hepatic Autophagy Deficiency Compromises Farnesoid X Receptor Functionality and Causes Cholestatic Injury.Hepatology (Baltimore, Md.) · 2019Article
- Dysregulation of ΔMolecular and cellular endocrinology · 2018Article
- Differential Feedback Regulation of Δ4-3-Oxosteroid 5β-Reductase Expression by Bile Acids.PloS one · 2017Article
- Navigation in bile acid chemical space: discovery of novel FXR and GPBAR1 ligands.Scientific reports · 2016Article
- [Role of farnesoid X receptor in rats with acute cholestatic hepatitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2016Article
- Bioenergetic cues shift FXR splicing towards FXRα2 to modulate hepatic lipolysis and fatty acid metabolism.Molecular metabolism · 2015Article
- Nuclear bile acid signaling through the farnesoid X receptor.Cellular and molecular life sciences : CMLS · 2015Review
- Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Transcriptional dynamics of bile salt export pump during pregnancy: mechanisms and implications in intrahepatic cholestasis of pregnancy.Hepatology (Baltimore, Md.) · 2014Article
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Authors and funding
7 authors.
Funding
Abstract
Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXRα1 and FXRα2, are predominantly expressed in human liver. We previously showed that human BSEP was isoform-dependently regulated by FXR and diminished with altered expression of FXRα1 and FXRα2 in patients with hepatocellular carcinoma. In this study, we demonstrate that FXRα1 and FXRα2 regulate human BSEP through two distinct FXR responsive elements (FXRE): IR1a and IR1b. As the predominant regulator, FXRα2 potently transactivated human BSEP through IR1a, while FXRα1 weakly transactivated human BSEP through a newly identified IR1b. Relative expression of FXRα1 and FXRα2 affected human BSEP expression in vitro and in vivo. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the binding and recruitment of FXRα1 and FXRα2 to IR1b and IR1a. Sequence analysis concluded that IR1b was completely conserved among species, whereas IR1a exhibited apparent differences across species. Sequence variations in IR1a were responsible for the observed species difference in BSEP transactivation by FXRα1 and FXRα2. In conclusion, FXR regulates BSEP in an isoform-dependent and species-specific manner through two distinct FXREs, and alteration of relative FXR isoform expression may be a potential mechanism for FXR to precisely regulate human BSEP in response to various physiological and pathological conditions.
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