ArticleGastroenterology2011
PXR prevents cholesterol gallstone disease by regulating biosynthesis and transport of bile salts.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 74 citations in OpenAlex.
- Nuclear receptor-mediated control of bile composition: implications for gallstone formation.Irish journal of medical science · 2026Review
- Bempedoic acid within the phase ternary diagram governing biliary cholesterol solubilization and gallstone risk.Journal of lipid research · 2026Review
- Mutation of PXR phosphorylation motif at Ser347 disrupts lipid and bile acid homeostasis in diet-induced metabolic dysfunction-associated steatohepatitis in mice.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- Advancements in Managing Choledocholithiasis and Acute Cholangitis in the Elderly: A Comprehensive Review.Cureus · 2025Review
- Metabolic disrupting chemicals in the intestine: the need for biologically relevant models: Zebrafish: what can we learn from this small environment-sensitive fish?FEBS open bio · 2024Review
- Article
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Review
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Gypenosides Prevent and Dissolve Cholesterol Gallstones by Modulating the Homeostasis of Cholesterol and Bile Acids.Frontiers in medicine · 2022Article
- Bile acid receptors and signaling crosstalk in the liver, gut and brain.Liver research (Beijing, China) · 2021Review
- The xenobiotic receptors PXR and CAR in liver physiology, an update.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- PXR: a center of transcriptional regulation in cancer.Acta pharmaceutica Sinica. B · 2020Review
- Current trends in drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2019Review
- Pregnane X Receptor Regulates Liver Size and Liver Cell Fate by Yes-Associated Protein Activation in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Dysregulation of ΔMolecular and cellular endocrinology · 2018Article
- Mouse models of gallstone disease.Current opinion in gastroenterology · 2018Review
- Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2018Review
- Recent advances in understanding and managing cholesterol gallstones.F1000Research · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsCholesterol gallstone disease (CGD) results from a biochemical imbalance of lipids and bile salts in the gallbladder bile. We investigated whether the xenobiotic receptor pregnane X receptor (PXR) has a role in pathogenesis of CGD.
methodsWild-type, PXR-null (PXR-/-), and CGD-sensitive C57L mice were placed on a lithogenic diet and then analyzed for CGD at the biochemical, histological, and gene-regulation levels.
resultsLoss of PXR sensitized mice to lithogenic diet-induced CGD, characterized by decreases in biliary concentrations of bile salts and phospholipids and an increases in the cholesterol saturation index and formation of cholesterol crystals. The decreased bile acid pool size in PXR-/- mice that received lithogenic diets was associated with reduced expression of cholesterol 7α-hydroxylase, the rate-limiting enzyme of cholesterol catabolism and bile acid formation. The reduced expression of cholesterol 7α-hydroxylase most likely resulted from activation of farnesoid X receptor and induction of fibroblast growth factor 15 in the intestine. In C57L mice given the PXR agonist, pregnenolone-16α-carbonitrile, or the herbal medicine, St John's wort, cholesterol precipitation was prevented by increases in concentrations of biliary bile salt and a reduced cholesterol saturation index. PXR prevented CGD via its coordinate regulation of the biosynthesis and transport of bile salts in the liver and intestine.
conclusionsPXR maintains biliary bile acid homeostasis and may be developed as a therapeutic target for CGD.
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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.