ArticleHepatology (Baltimore, Md.)2014
Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Comparative efficacy and safety of ursodeoxycholic acid, fibrates, and combination therapy in primary biliary cholangitis: an umbrella meta-analysis of meta-analyses.Frontiers in pharmacology · 2026Pooled it
- Efficacy of fibrates in the treatment of primary biliary cholangitis: a meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Fibrates for the treatment of cholestatic itch (FITCH): study protocol for a randomized controlled trial.Trials · 2017Trial
- Fenofibrate discontinuation and the association with clinical outcomes in primary biliary cholangitis patients receiving combination therapy.International journal of clinical pharmacy · 2026Article
- Multi-omics Mendelian randomization and experimental validation identify PRKAB1 as a regulator of phosphatidylcholine metabolism in IBD.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- New therapies for primary biliary cholangitis.Hepatology international · 2026Review
- Review Article: Targeting Peroxisome Proliferator-Activated Receptors in Primary Biliary Cholangitis.Alimentary pharmacology & therapeutics · 2026Review
- A Rare Nonsense Mutation in theJournal of clinical medicine · 2026Article
- Cholestatic and autoimmune liver diseases, bile duct injury, oxidative stress, and therapeutic strategies.Frontiers in physiology · 2026Review
- Single-Nuclei RNA Sequencing Shows the Engagement of PPAR-Delta Target Genes Primarily in Hepatocytes and Cholangiocytes by the Selective PPAR-Delta Agonist Seladelpar.PPAR research · 2025Article
- Treatment of primary sclerosing cholangitis combined with inflammatory bowel disease.Intestinal research · 2023Review
- Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.Frontiers in pharmacology · 2023Review
- Article
- Obeticholic Acid for Primary Biliary Cholangitis.Biomedicines · 2022Review
- Update on the Pharmacological Treatment of Primary Biliary Cholangitis.Biomedicines · 2022Review
- Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis.Frontiers in pharmacology · 2022Article
- PPARα: A potential therapeutic target of cholestasis.Frontiers in pharmacology · 2022Review
- Adjunct Fenofibrate Up-regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis.Hepatology communications · 2021Article
- Article
- Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities.Journal of gastroenterology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledMultidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 (MDR3/ABCB4) is a critical determinant of biliary phosphatidylcholine (PC) secretion. Clinically, mutations and partial deficiencies in MDR3 result in cholestatic liver injury. Thus, MDR3 is a potential therapeutic target for cholestatic liver disease. Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) α ligand that has antiinflammatory actions and regulates bile acid detoxification. Here we examined the mechanism by which fenofibrate regulates MDR3 gene expression. Fenofibrate significantly up-regulated MDR3 messenger RNA (mRNA) and protein expression in primary cultured human hepatocytes, and stimulated MDR3 promoter activity in HepG2 cells. In silico analysis of 5'-upstream region of human MDR3 gene revealed a number of PPARα response elements (PPRE). Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated specific binding of PPARα to the human MDR3 promoter. Targeted mutagenesis of three novel PPREs reduced inducibility of the MDR3 promoter by fenofibrate. In collagen sandwich cultured rat hepatocytes, treatment with fenofibrate increased secretion of fluorescent PC into bile canaliculi.
conclusionFenofibrate transactivates MDR3 gene transcription by way of the binding of PPARα to three novel and functionally critical PPREs in the MDR3 promoter. Fenofibrate treatment further stimulates biliary phosphatidylcholine secretion in rat hepatocytes, thereby providing a functional correlate. We have established a molecular mechanism that may contribute to the beneficial use of fenofibrate therapy in human 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.