ArticleBiochemical pharmacology2015
Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 54 citations in OpenAlex.
- Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tetrabromobisphenol A: MAK Value Documentation - Translation of the German version from 2023.The MAK collection for occupational health and safety · 2025Review
- Constitutive androstane receptor, liver pathophysiology and chemical contaminants: current evidence and perspectives.Frontiers in endocrinology · 2025Review
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Clinical Relevance of the Constitutive Androstane Receptor.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Individualized pathway activity algorithm identifies oncogenic pathways in pan-cancer analysis.EBioMedicine · 2022Article
- Human constitutive androstane receptor represses liver cancer development and hepatoma cell proliferation by inhibiting erythropoietin signaling.The Journal of biological chemistry · 2022Article
- Molecular basis of crosstalk in nuclear receptors: heterodimerization between PXR and CAR and the implication in gene regulation.Nucleic acids research · 2022Article
- Phenobarbital Induces SLC13A5 Expression through Activation of PXR but Not CAR in Human Primary Hepatocytes.Cells · 2021Article
- Molecular Mechanisms of the SLC13A5 Gene Transcription.Metabolites · 2021Review
- Metamizole is a Moderate Cytochrome P450 Inducer Via the Constitutive Androstane Receptor and a Weak Inhibitor of CYP1A2.Clinical pharmacology and therapeutics · 2021Article
- Differential effects on human cytochromes P450 by CRISPR/Cas9-induced genetic knockout of cytochrome P450 reductase and cytochrome b5 in HepaRG cells.Scientific reports · 2021Article
- Primary hepatocytes isolated from human and porcine donors display similar patterns of cytochrome p450 expression following exposure to prototypical activators of AhR, CAR and PXR.Current research in toxicology · 2021Article
- β-catenin signaling, the constitutive androstane receptor and their mutual interactions.Archives of toxicology · 2020Review
- Constitutive Androstane Receptor: A Peripheral and a Neurovascular Stress or Environmental Sensor.Cells · 2020Review
- Mechanistic Insights of Phenobarbital-Mediated Activation of Human but Not Mouse Pregnane X Receptor.Molecular pharmacology · 2019Article
- In vivo genome-wide binding interactions of mouse and human constitutive androstane receptors reveal novel gene targets.Nucleic acids research · 2018Article
- The Roles of Xenobiotic Receptors: Beyond Chemical Disposition.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The constitutive androstane receptor (CAR) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. Most functions of CAR however were defined from animal studies. Given the known species difference of CAR and the significant cross-talk between CAR and the pregnane X receptor (PXR), it is extremely difficult to decipher the exact role of human CAR (hCAR) in gene regulation, relying predominantly on pharmacological manipulations. Here, utilizing a newly generated hCAR-knockout (KO) HepaRG cell line, we carried out RNA-seq analysis of the global transcriptomes in wild-type (WT) and hCAR-KO HepaRG cells treated with CITCO, a selective hCAR agonist, phenobarbital (PB), a dual activator of hCAR and hPXR, or vehicle control. Real-time PCR assays in separate experiments were used to validate RNA-seq findings. Our results indicate that genes encoding drug-metabolizing enzymes are among the main clusters altered by both CITCO and PB. Specifically, CITCO significantly changed the expression of 135 genes in an hCAR-dependent manner, while PB altered the expression of 227 genes in WT cells of which 94 were simultaneously modulated in both cell lines reflecting dual effects of PB on hCAR/PXR. Notably, we found that many genes promoting cell proliferation and tumorigenesis were up-regulated in hCAR-KO cells, suggesting that hCAR may play an important role in cell growth that differs from mouse CAR. Together, our results reveal both novel and known targets of hCAR and support the role of hCAR in maintaining the homeostasis of metabolism and cell proliferation in the liver.
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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.