ArticleThe Journal of clinical investigation2003
Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 381 citations in OpenAlex.
- Bile Acids and FXR: Novel Targets for Liver Diseases.Frontiers in medicine · 2020Pooled it
- Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production.Clinical and molecular hepatology · 2026Trial
- Roles of FXR in Lipid Biochemistry within Hepatocellular Carcinoma Using MALDI MSI.Journal of the American Society for Mass Spectrometry · 2026Article
- Network Pharmacology Analysis Reveals Multi-Target Hepatoprotective Mechanisms of a Multi-Component Pharmacopuncture Against Ephedra-Associated Liver Injury with Implications for Mitochondrial Quality Control.Medicina (Kaunas, Lithuania) · 2026Article
- Alveolar Type 2 Cell Dysfunction Is Associated with Bile Acid Alterations in Experimental Hepatopulmonary Syndrome.American journal of respiratory cell and molecular biology · 2026Article
- Dysbiosis in the Gut-Liver Axis Is Associated With Low Bone Mass During Murine Cholestasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs.Cellular & molecular immunology · 2025Article
- Evaluation of FXR Activity in Pollutants Identified in Sewage Sludge and SubsequentEnvironmental health perspectives · 2025Article
- Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development.Pharmacological reviews · 2024Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.Journal of natural medicines · 2024Article
- Chishao (Frontiers in pharmacology · 2024Article
- Article
- Bile Acids and Biliary Fibrosis.Cells · 2023Review
- The role of the farnesoid X receptor in kidney health and disease: a potential therapeutic target in kidney diseases.Experimental & molecular medicine · 2023Review
- Role of FXR in Renal Physiology and Kidney Diseases.International journal of molecular sciences · 2023Review
- Bile acid receptors and renal regulation of water homeostasis.Frontiers in physiology · 2023Review
- The role of hepatic microenvironment in hepatic fibrosis development.Annals of medicine · 2022Review
- Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis.JHEP reports : innovation in hepatology · 2022Article
- NOX as a Therapeutic Target in Liver Disease.Antioxidants (Basel, Switzerland) · 2022Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Farnesoid X receptor (FXR) is a bile acid-activated transcription factor that is a member of the nuclear hormone receptor superfamily. Fxr-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease.
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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.