ArticleJournal of lipid research2010
Retinoic acid represses CYP7A1 expression in human hepatocytes and HepG2 cells by FXR/RXR-dependent and independent mechanisms.
Article in Journal of lipid research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
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
50 citing papers in PubMed, 84 citations in OpenAlex.
- Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity.Journal of clinical pharmacology · 2023Trial
- Does In Vitro Cytochrome P450 Downregulation Translate to In Vivo Drug-Drug Interactions? Preclinical and Clinical Studies With 13-cis-Retinoic Acid.Clinical and translational science · 2019Trial
- Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis: A Human Pilot Study.Journal of clinical gastroenterology · 2017Trial
- Alterations in Lipid Metabolism and Hepatopancreatic Lipidomics Induced by Microcystin-LR Exposure in Common Carp (Animals : an open access journal from MDPI · 2025Article
- Deficiency of Epithelial PIEZO1 Alleviates Liver Steatosis Induced by High-Fat Diet in Mice.International journal of biological sciences · 2025Article
- The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease.Hepatology communications · 2024Review
- CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.International journal of molecular sciences · 2023Article
- Curcumin and Its Supramolecular Complex with Disodium Glycyrrhizinate as Potential Drugs for the Liver Fluke Infection Caused byPathogens (Basel, Switzerland) · 2023Article
- Mechanisms of Feedback Regulation of Vitamin A Metabolism.Nutrients · 2022Review
- Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer.Frontiers in pharmacology · 2022Review
- Up-regulation of the manganese transporter SLC30A10 by hypoxia-inducible factors defines a homeostatic response to manganese toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Role of Fibroblast Growth Factor 19 in Hepatocellular Carcinoma.The American journal of pathology · 2021Review
- The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities.Journal of clinical medicine · 2021Review
- The Gut-Liver Axis in Cholestatic Liver Diseases.Nutrients · 2021Review
- Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities.Journal of gastroenterology · 2020Review
- Fermentable fibers induce rapid macro- and micronutrient depletion in Toll-like receptor 5-deficient mice.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Retinoids Repress Human Cardiovascular Cell Calcification With Evidence for Distinct Selective Retinoid Modulator Effects.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Farnesoid X receptor and bile acids regulate vitamin A storage.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cholesterol 7alpha-hydroxylase (CYP7A1) plays a key role in maintaining lipid and bile salt homeostasis as it is the rate-limiting enzyme converting cholesterol to bile acids. Deficiency of CYP7A1 leads to hyperlipidemia in man and mouse. Hyperlipidemia is often seen in patients when treated with high-dose retinoic acid (RA), but the molecular mechanisms remain elusive. Our present study revealed that CYP7A1 mRNA expression is greatly repressed by RA in both human hepatocytes and HepG2 cells where increased fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) expressions were also observed, suggesting farnesoid X receptor (FXR) and retinoid X receptor (RXR) were activated. Promoter reporter assays demonstrate that all-trans RA (atRA) specifically activated FXR/RXR. However, detailed molecular analyses indicate that this activation is through RXR, whose ligand is 9-cis RA. Knocking down of FXR or RXRalpha by small interference RNA (siRNA) in human hepatocytes increased CYP7A1 basal expression, but the repressive effect of atRA persisted, suggesting there are also FXR/RXR-independent mechanisms mediating atRA repression of CYP7A1 expression. Chromatin immunoprecipitation (ChIP) assay and cell transfection results indicate that PGC-1alpha plays a role in the FXR/RXR-independent mechanism. Our findings may provide a potential explanation for hyperlipidemic side effects observed in some patients treated with high-dose RA.
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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.