ArticleThe Journal of clinical investigation2015
Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- The pathogenesis of liver fibrosis in Wilson's disease: hepatocyte injury and regulation mediated by copper metabolism dysregulation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Copper and hepatic lipid dysregulation: Mechanisms and implications.World journal of hepatology · 2025Review
- Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease.Hepatology communications · 2025Article
- Comparative review of copper-associated chronic hepatitis in dogs and Wilson disease in humans.Frontiers in veterinary science · 2025Review
- Navigating the CRISPR/Cas Landscape for Enhanced Diagnosis and Treatment of Wilson's Disease.Cells · 2024Review
- Construction of a nomogram for predicting compensated cirrhosis with Wilson's disease based on non-invasive indicators.BMC medical imaging · 2024Article
- Hepatic oxylipin profiles in mouse models of Wilson disease: New insights into early hepatic manifestations.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.Current neuropharmacology · 2024Review
- Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease.Pharmacology & therapeutics · 2023Review
- RNA methylations in hepatic fibrosis, a gradually emerging new treatment strategy.Cell & bioscience · 2023Review
- Companion animal organoid technology to advance veterinary regenerative medicine.Frontiers in veterinary science · 2023Review
- Retinoids rescue ceruloplasmin secretion and alleviate oxidative stress in Wilson's disease-specific hepatocytes.Human molecular genetics · 2022Article
- ATP7B-Deficient Hepatocytes Reveal the Importance of Protein Misfolding Induced at Low Copper Concentration.Cells · 2022Article
- Oxysterol misbalance critically contributes to Wilson disease pathogenesis.Science advances · 2022Article
- Wilson Disease: Update on Pathophysiology and Treatment.Frontiers in cell and developmental biology · 2022Review
- Hepatic Steatosis in the Mouse Model of Wilson Disease Coincides with a Muted Inflammatory Response.The American journal of pathology · 2022Article
- Hepatic drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure.Pharmacological reports : PR · 2021Article
- Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease.Biomedicines · 2021Review
- Systemic deletion of Atp7b modifies the hepatocytes' response to copper overload in the mouse models of Wilson disease.Scientific reports · 2021Article
- COMMD1 Exemplifies the Power of Inbred Dogs to Dissect Genetic Causes of Rare Copper-Related Disorders.Animals : an open access journal from MDPI · 2021Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.
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