ArticleJournal of lipid research2008
Liver receptor homolog 1 transcriptionally regulates human bile salt export pump expression.
Article in Journal of lipid research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
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Who cites it
29 citing papers in PubMed, 66 citations in OpenAlex.
- Exploring the Expanding Role of Nuclear Receptor LRH-1/NR5A2 in Cell Biology and Immunity.International journal of cell biology · 2026Review
- A minimal bile salt excretory pump promoter allows bile acid-driven physiological regulation of transgene expression from a gene therapy vector.Cell & bioscience · 2022Article
- The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.International journal of molecular sciences · 2021Review
- Bile acid transporter-mediated oral drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2020Review
- A Change in Bile Flow: Looking Beyond Transporter Inhibition in the Development of Drug-induced Cholestasis.Current drug metabolism · 2019Review
- Mechanistic insights into geniposide regulation of bile salt export pump (BSEP) expression.RSC advances · 2018Article
- ABCMdb reloaded: updates on mutations in ATP binding cassette proteins.Database : the journal of biological databases and curation · 2017Article
- Differential Feedback Regulation of Δ4-3-Oxosteroid 5β-Reductase Expression by Bile Acids.PloS one · 2017Article
- Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Nuclear receptor NR5A2 controls neural stem cell fate decisions during development.Nature communications · 2016Article
- Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1.BMB reports · 2015Article
- 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
- Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations.Molecular aspects of medicine · 2014Review
- Clinical application of transcriptional activators of bile salt transporters.Molecular aspects of medicine · 2014Review
- The role of bile salt export pump gene repression in drug-induced cholestatic liver toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Human FXR regulates SHP expression through direct binding to an LRH-1 binding site, independent of an IR-1 and LRH-1.PloS one · 2014Article
- Mechanistic insights into isoform-dependent and species-specific regulation of bile salt export pump by farnesoid X receptor.Journal of lipid research · 2013Article
- Bile formation and secretion.Comprehensive Physiology · 2013Review
- Bile salt export pump is dysregulated with altered farnesoid X receptor isoform expression in patients with hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The metabolic conversion of cholesterol into bile acids in liver is initiated by the rate-limiting cholesterol 7 alpha-hydroxylase (CYP7A1), whereas the bile salt export pump (BSEP) is responsible for the canalicular secretion of bile acids. Liver receptor homolog 1 (LRH-1) is a key transcriptional factor required for the hepatic expression of CYP7A1. We hypothesized that LRH-1 was also involved in the transcriptional regulation of BSEP. In support of our hypothesis, we found that overexpression of LRH-1 induced, whereas knockdown of LRH-1 decreased, BSEP expression. Consistent with its role in transcriptional regulation, LRH-1 dose-dependently transactivated the BSEP promoter. In addition, such transactivation by LRH-1 was required for maximal induction of BSEP expression through the bile acid/farnesoid X receptor (FXR) activation pathway. Bioinformatic and mutational analysis led to the identification of a functional liver receptor homolog 1-responsive element (LRHRE) in the BSEP promoter. Specific binding of LRH-1 to the LRHRE and recruitment of LRH-1 to the BSEP promoter were demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively. In conclusion, LRH-1 transcriptionally activated the BSEP promoter and functioned as a modulator in bile acid/FXR-mediated BSEP regulation. These results suggest that LRH-1 plays a supporting role to FXR in maintaining hepatic bile acid levels by coordinately regulating CYP7A1 and BSEP for bile acid synthesis and elimination, respectively.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.