ArticleLiver international : official journal of the International Association for the Study of the Liver2025
Liver GPBAR1 Associates With Immune Dysfunction in Primary Sclerosing Cholangitis and Its Activation Attenuates Cholestasis in Abcb4-/- Mice.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A bibliometric analysis of global research status and trends in irritable bowel syndrome and gut microbiota metabolites.Frontiers in microbiology · 2025Pooled it
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Research Progress on the Mechanism and Targeted Intervention of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1)-Mediated "Inflammation-Apoptosis-Metabolism-Microcirculation" Regulatory Network in Hepatitis B-Associated Liver Failure.Drug design, development and therapy · 2026Review
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- Multi-omics tests identify novel shared genetic mechanisms of primary biliary cholestasis and sarcopenia.Scientific reports · 2025Article
- Harnessing the Estradienone Scaffold to Develop Dual GPBAR1 and LIFR Modulators for Liver Fibrosis.Journal of medicinal chemistry · 2025Article
- Autoimmunity in MASLD: Focus on autoantibodies, anti-apolipoprotein A1 IgG and G protein-coupled receptors.European journal of clinical investigation · 2025Review
- Leukemia inhibitory factor promotes human cholangiopathies, and its inhibition improves cholestasis in Abcb4-/- mice.Hepatology communications · 2025Article
- Targeting the gut-liver axis in cholangiocarcinoma: mechanisms, therapeutic advances, and future directions.Frontiers in oncology · 2025Review
- Macrophage heterogeneity in liver fibrosis.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
BACKGROUND AND
aimsPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterised by progressive biliary inflammation and fibrosis, leading to liver cirrhosis and cholangiocarcinoma. GPBAR1 (TGR5) is a G protein-coupled receptor for secondary bile acids. In this study, we have examined the therapeutic potential of BAR501, a selective GPBAR1 agonist in a PSC model.
methodsSingle-cell analysis of healthy human liver samples and gene expression analysis of PSC liver samples were conducted. In vitro studies on a human cholangiocyte cell line (NHC), U937 and human hepatic stellate cells (hSteCs) were performed. Additionally, Abcb4
resultsSingle-cell analysis demonstrated that GPBAR1 is expressed by macrophages, NK cells, sinusoidal cells and to a lesser extent by cholangiocytes. Total liver expression of GPBAR1 increases in PSC patients compared to that in healthy controls and positively correlates with markers for monocytes and NK cells and cytokeratin 19. In vitro treatment of NHCs with BAR501 reversed the acquisition of a pro-inflammatory phenotype and the downregulation of GPBAR1 expression promoted by LPS in an NF-κB-dependent manner. Treating Abcb4
conclusionsOur study provides evidence for the therapeutic potential of selective GPBAR1 agonists in intestinal inflammation-associated cholestasis, warranting the evaluation of BAR501 in PSC patients.
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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 Socratic graph.