Publication for Nr1i3 and Nr1i2

Species Symbol Function* Entrez Gene ID* Other ID Gene
coexpression		 CoexViewer
mmu Nr1i3 nuclear receptor subfamily 1, group I, member 3 12355 [link]
mmu Nr1i2 nuclear receptor subfamily 1, group I, member 2 18171

Pubmed ID Priority Text
24998970 0.99 CAR/PXR could result in increased SREBP1 gene expression.
0.99 CAR and PXR can transcriptionally activate the anti-lipogenic gene Insig-1, consequently leading to reduced SREBP1 activity and decreased SREBP1 target gene expression such as FAS.
0.98 constitutive androstane receptor (CAR) and the pregnane-xenobiotic receptor (PXR).
0.98 CAR and PXR are capable of binding, potentially sequestering and altering the transcriptional activity of FOXO1.
0.98 PXR activation, but activated CAR can also bind to the Cyp3a11 response element and drive its expression, albeit, at lower levels.
0.98 CAR/PXR activation suppresses FoxO1-insulin response sequence (IRS) binding activity resulting in decreased gluconeogenesis and hence the lowered fasting blood glucose levels seen in CD + Aroclor 1260 groups.
0.97 CAR/PXR could contribute to the observed decrease in % fat composition in HFD +Aroclor 1260 groups.
0.97 CAR/PXR target genes as compared to CD consumption and it was only HFD-fed mice exposed to Aroclor 1260 that exhibited liver injury.
0.97 CAR/PXR activation by PCBs, and therefore attenuates the protective effects of these receptors against PCB toxicity with the net result being increased liver injury only in Aroclor 1260 + HFD co-exposed animals.
0.97 CAR, PXR and AhR target genes.
0.96 PXR and CAR are critically involved in xenobiotic metabolism and drug disposition, but recent studies demonstrated the importance of CAR and PXR regulation on physiological processes such as glucose and lipid metabolism, and this could impact NASH.
0.96 CAR/PXR, hence the possible obesity-protective effects seen in the HFD-fed mice exposed to Aroclor 1260.
0.95 CAR and PXR), bind.
0.94 PXR target) and Cyp2b10 (CAR target), were induced by Aroclor 1260 exposure in both CD and HFD-fed mice.
0.94 CAR/PXR protect against PCB toxicity in a low fat diet setting.
0.94 CAR/PXR and AhR activation as potential mode(s) of action of this PCB mixture in NASH.
0.94 CAR and PXR activation could be protective against PCB-mediated toxicity but HFD consumption may blunt this protection.
0.93 CAR and PXR.
0.93 PXR and CAR activation and other implicated mechanisms; and iii) effects observed with Aroclor 1260 administration are dependent on PCB dose.
0.93 CAR or PXR directly or indirectly.
0.93 CAR and PXR and to a lesser extent AhR, suggesting congener composition and exposure levels to be critical in determining a mixture's mode(s) of actions.
0.90 CAR/PXR are present in much higher concentrations than those that activate AhR and the receptor based-effects of Aroclor 1260 at the lower dose are likely to be mediated primarily through CAR/PXR activation.
0.87 CAR, PXR and AhR target genes
0.74 CAR rather than PXR.
0.61 CAR target gene), (B) Cyp3a11 (PXR target gene), (C) Cyp1a2 (AhR target gene) and (D) PEPCK-1 (an indirect target of CAR and PXR).
22889594 0.99 PXR and CAR can physically bind to FoxO1 and suppress its transcriptional activity by preventing its binding to the insulin response sequence in the gluconeogenic enzyme gene promoters.
0.98 Pregnane X receptor (PXR/SXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3), two members of the superfamily of nuclear receptors, have been well recognized as "xenobiotic sensors" that transcriptionally regulate the expression of Phase I and Phase II drug/xenobiotic metabolizing enzymes and transporters.
0.98 PXR and CAR may suppress the gluconeogenic gene expression by targeting several key transcriptional factors involved in gluconeogenesis.
0.98 PXR and CAR, hepatocytes are able to maintain necessary NADPH levels and sustain a protective function of drug metabolism under energy-restricted conditions.
0.97 pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors.
0.97 PXR and CAR also have endobiotic functions that impact glucose and lipid metabolism, as well as the pathogenesis of metabolic diseases.
0.97 PXR and CAR not only regulate the transcription of drug-metabolizing enzymes and transporters, but also orchestrate energy metabolism and immune responses to accommodate stresses caused by xenobiotic exposures.
0.97 PXR and CAR in regulating energy homeostasis under both physiological and pathological conditions.
0.96 PXR and CAR in the treatment of metabolic disorders, such as obesity, type 2 diabetes (T2D), dyslipidemia, and atherosclerosis, have been suggested in animal models.
0.96 PXR/CAR and gluconeogenic pathway may represent a cellular adaptation mechanism to cope with energy deficiency in various pathophysiological conditions.
0.96 CAR activation on lipid metabolism, activation of PXR seemed to promote dyslipidemia.
0.95 PXR/CAR has gained increased attention.
0.94 PXR and CAR modulators, it is hoped that these two "xenobiotic receptors" can be harnessed for therapeutic potentials in managing metabolic diseases.
0.94 PXR and CAR, including those implicated in metabolic diseases, are expected to drive these "old" xenobiotic receptors into a new era.
0.92 PXR and CAR regulate not only drug metabolism but also energy homeostasis and immune response, which may establish PXR and CAR as potential therapeutic targets for metabolic diseases.
0.91 PXR and CAR in regulating drug metabolism, pharmaceutical agents targeting PXR/CAR have the potential of causing untoward drug-drug interactions.
0.82 PXR and CAR modulators may provide novel therapeutic tools for the management of metabolic disorders.
0.81 PXR and CAR as potential therapeutic targets for metabolic diseases
0.76 PXR and CAR in energy homeostasis and immune regulation, and the implications of these functions in metabolic diseases.
0.65 PXR and CAR in metabolic disease
0.61 PXR and CAR ligands has been continuously growing in recent years and these small molecules with diverse structures may serve as starting points for future development of novel PXR and CAR modulators with therapeutic potentials (Tables 1 and 2).
0.51 PXR and CAR for metabolic diseases
29725048 0.99 CAR and PXR, nuclear transcription factors.
0.98 CAR/PXR, the transcription factors for NQO1 and CYP3A44/3A41, respectively.
0.98 constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor (PPARalpha) and nuclear factor-E2-related factor 2 (Nrf2) are well-characterized xenobiotic-activated transcription factors in liver that regulate the induction of drug metabolizing enzymes (DMEs) and transporters such as CYP450s and NQO.
0.98 CAR and PXR mRNA levels were associated with GNMT expression upon AAI stimulation, suggesting the involvement of GNMT in the regulation of transcription factors.
0.98 CAR/PXR and enhance subsequent NQO1 and CYP3A44/3A41 transcriptions, respectively.
0.97 CAR/PXR/CYP3A44/3A41 transcriptions and alleviated kidney injury upon AAI treatment.
0.97 CAR and GNMT-PXR markedly increased (Fig. 7d).
0.97 CAR and GNMT-PXR were higher at low AAI concentration than at higher concentration (Fig. 7f), resulting in increases in CYP3A44/3A41 mRNA levels (Fig. 4g and h) and minor kidney injuries (Fig. 4c).
0.97 CAR and GNMT-PXR, resulting in a reduction of CYP3A44/CYP3A41 transcripts.
0.97 CAR/PXR transcription in nucleus, CYP3A44/CYP3A41 mRNA levels were thus upregulated, and the kidneys mildly damaged (Fig. 8b).
0.97 CAR/PXR/CYP3A44/3A41 transcription and decreasing Nrf2/NQO1 transcription in female hepatocytes.
0.96 CAR/PXR and CYP3A44/3A41 transcriptions and decreasing NRF2/NQO1 transcriptions in female mouse hepatocytes.
0.96 PXR and CAR signaling pathways were inhibited in the liver of WT female mice treated with 5 mg/kg/day AAI, 5 days a week for 3 weeks (Supplementary Fig. S8).
0.96 CAR/PXR mRNA levels were significantly decreased in AAI-treated WTL mice and increased in AAI-treated Tg mice (Fig. 6e,f).
0.95 CAR/PXR/CYP3A44/3A41 transcriptions and reducing Nrf2/NQO1 transcriptions.
0.95 CAR and PXR promoter DNAs (GNMT-CAR and GNMT-PXR) decreased (Fig. 7b,c).
0.94 CAR and GNMT-PXR levels slightly increased, but were still lower than that of GNMT-Nrf2 (Fig. 7e).
0.71 PXR and CAR genes in the nucleus upon AAI stimulation, chromatin immunoprecipitation (ChIP) assays were performed (Fig. 7a).
27113289 0.98 PXR and CAR are well known xenobiotic-sensing transcription factors that trans-activate a large battery of genes involved in xenobiotic metabolism and transport (together called "drug-processing genes" [DPGs]).
0.98 PXR and CAR are well known to up-regulate the transcription of numerous DPGs involved in phase-I and phase-II drug metabolism as well as transport.
0.98 PXR and CAR lead to the up-regulation of many common DPGs in liver.
0.98 PXR, CAR, estrogen receptor, interleukin (IL) receptor 10a, Cxcl12, insulin signaling, as well as the interaction between PXR/CAR with the nuclear receptor coactivator a (Ncoa) (Table S3-1).
0.98 PXR and CAR activation on the expression of genes related to histone acetylation and deacetylation is shown in Figure 13B.
0.98 CAR, PXR also binds to the direct-repeat 4 (DR-4) like motifs, which are the most prevalent PXR-DNA binding response elements in the mouse liver.
0.98 PXR and CAR ligands appear to down-regulate multiple genes involved in the pro-inflammatory response.
0.98 CAR activator phenobarbital (which can also activate PXR), whereas similar results were observed in livers of mice treated with TCPOBOP (Figure 2).
0.97 pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known xenobiotic-sensing nuclear receptors with overlapping functions.
0.97 PXR and CAR in regulating the DPGs and the subsequent modifications on the metabolism and disposition of xenobiotics and endobiotics, these nuclear receptors are responsible for many adverse drug reactions.
0.97 PXR and CAR leads to both common and unique changes in target genes.
0.97 PXR and CAR ligands appear to be an up-regulation of the Cyp3a genes, and especially through increasing the Cyp3a11 isoform.
0.97 CAR ligand influences the Akr expression of the Akrs more than the PXR ligand, and the overall effect of CAR activation is up-regulation of these Akrs.
0.97 PXR or CAR activation.
0.97 PXR and CAR signaling in liver.
0.97 CAR and other receptors such as AhR, PXR, and PPARalpha, because the activators for these other receptors can also activate CAR-signaling.
0.97 CAR by TCPOBOP up-regulates the AhR-target genes Cyp1a as well as many PXR-target genes, however, it actually down-regulates the PPARalpha-target genes in the Cyp4a family.
0.97 PXR and CAR activation by lithocholic acid in wild-type and PXR/CAR-null mice has shown that CAR predominantly mediates the induction of Cyp3a11 and Mrp3, whereas PXR is the major regulator of Oatp1a4.
0.97 CAR and PXR activators) in livers of hPXR/hCAR-humanized mice.
0.96 PXR- and CAR-target Gene Signatures in the Mouse Liver Transcriptome
0.96 PXR and CAR are well-known to enhance drug metabolism, recent studies in the literature have also unveiled their novel functions in intermediary metabolism.
0.96 PXR and CAR share high similarity in their transcriptional activities.
0.96 CAR ligand appears to have a more prominent influence on Cyp2 gene expression than the PXR ligand, and the majority of the abundantly expressed Cyp2a-c genes were up-regulated by the CAR ligand, whereas the highest expressed Cyp2 isoform Cyp2e1 was actually down-regulated by the CAR ligand.
0.96 PXR and CAR share many common targets, among which xenobiotic metabolism is the top category, but genes involved in inflammation, iron homeostasis, and retinoic acid metabolism are also co-regulated.
0.96 PXR and CAR also have unique target gene profiles, most notably, CAR up-regulates many genes involved in cell proliferation, bile acid synthesis and composition, as well as epigenetic remodeling, whereas PXR has less effect on these pathways.
0.96 PXR and CAR are well-known xenobiotic-sensing receptors, the present study demonstrates that many other pathways appear to be regulated by PXR and CAR ligands.
0.96 PXR and CAR signaling at various physiological and pathophysiological conditions.
0.95 PXR and CAR in mouse liver following pharmacological activation using their prototypical ligands.
0.95 PXR- and CAR-target DPGs in the liver on a transcriptomic scale.
0.95 PXR and CAR are well known xenobiotic-sensing nuclear receptors, the mRNA expression of all DPGs (including 318 phase-I and 92 phase-II drug-metabolizing enzymes as well as 519 transporters) was examined in detail regarding their common and different transcriptional responses following PCN or TCPOBOP treatment.
0.95 PXR and CAR ligands on hepatic DPG expression, the cumulative FPKM of all differentially regulated DPGs was calculated as shown in Figure 2B-F. The cumulative hepatic mRNAs of all differentially regulated DPGs, phase-I and -II enzymes, and efflux transporters were all up-regulated by both PCN and TCPOBOP, and to a greater extent by TCPOBOP (Figure 2B-E).
0.95 PXR and CAR agonists on the expression of the Cyp3a family members is shown in Figure 4A.
0.95 CAR ligand has a more prominent influence on the bile acid synthesis pathway than the PXR ligand.
0.95 PXR and CAR.
0.95 PXR and CAR ligands has been characterized in mice using branched DNA amplification (bDNA) assays.
0.95 PXR and CAR receptors in mouse liver following chemical activation using their prototypical ligands.
0.94 PXR- and CAR-mediated regulation of all DPGs in liver.
0.93 PXR and CAR signaling at various physiological and pathophysiological conditions.
0.92 PXR- and CAR-target genes in mouse liver.
0.92 PXR- and CAR-targeted signaling pathways in liver following the chemical activation of these nuclear receptors, pathway analyses were performed in the common and unique PXR- and CAR-target genes.
0.92 PXR or CAR.
0.92 PXR- and CAR-mediated up-regulation in the efflux transporters Mrp2-4, as well as the uptake transporter Oatp1a4 in liver.
0.91 PXR/CAR-mediated pharmacokinetic responses.
0.91 PXR and CAR share marked similarities regarding their transcriptional activities and target genes.
0.87 PXR and CAR target genes and signaling pathways in liver.
0.87 PXR activation appeared to overlap with the aryl hydrocarbon receptor signaling, whereas CAR activation appeared to overlap with the farnesoid X receptor signaling, acute-phase response, and mitochondrial dysfunction.
0.86 PXR and CAR target genes in the mouse transcriptome, with a primary focus on critical genes involved in xenobiotic biotransformation and epigenetics.
0.83 CAR ligand is likely to be an increase in Abc-mediated efflux, whereas the PXR ligand appears to have less effect.
0.80 PXR and CAR on the regulation of DPGs, the expression of various phase-I and -II drug-metabolizing enzymes, transporters, as well as essential nuclear receptors and/or xenobiotic-sensing transcription factors was examined as shown in Figure 3 to Figure 12.
23626729 0.98 PXR activation leads quiescent (G0 phase of cell cycle) hepatocytes to enter G1 phase, making hepatocytes more sensitive to CAR or PPARalpha activators for cell cycle progression.
0.97 pregnane X receptor (PXR, NR1I2) and constitutive active/androstane receptor (CAR, NR1I3) are members of the NR1I subfamily of the nuclear receptor gene superfamily.
0.97 PXR enhances the CAR-mediated hepatocyte proliferation independent of the type of CAR activators.
0.97 CAR is known as a key transcription factor in the xenobiotic-induced hepatocyte proliferation while it remains unclear whether PXR has such a function.
0.97 PXR, when activated, has a very unique function in the cell cycle of murine hepatocytes, enhancing the CAR-mediated hepatocyte proliferation without inducing the proliferation by itself.
0.97 PXR significantly enhanced the CAR- or PPARalpha-mediated proliferation of murine hepatocytes.
0.96 Constitutive Active/Androstane Receptor (CAR) or Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) Is Enhanced by Pregnane X Receptor (PXR) Activation in Mice
0.96 pregnane X receptor (PXR), constitutive active/androstane receptor (CAR) and peroxisome proliferator-activated receptor alpha (PPARalpha) play pivotal roles in the metabolic functions of the liver such as xenobiotics detoxification and energy metabolism.
0.96 CAR activation with TCPOBOP or phenobarbital in wild-type mice but not in PXR-deficient mice.
0.96 CAR or PPARalpha is enhanced by PXR co-activation despite that PXR activation alone does not cause the cell proliferation in mouse livers.
0.96 PXR does not simply enhance the CAR- or PPARalpha-mediated gene transcription (or repression) in hepatocytes.
0.96 PXR co-activation enhances the CAR- or PPARalpha-related cell proliferation in mouse livers.
0.96 PXR activation alone showed no effects on the expression of cell proliferation-related genes investigated such as Ccnb1, suggesting that PXR does not induce hepatocyte division in contrast to CAR and PPARalpha.
0.95 PXR is activated by a wide range of xenobiotics far more than CAR, the elucidation of the PXR's ability to initiate hepatocyte proliferation is quite important for the chemical safety evaluation.
0.95 PXR activation does not continuously enhances the CAR-mediated hepatocyte proliferation and rather it enhances the early stage of the proliferation.
0.94 PXR and CAR work in concert to protect the body against harmful xenobiotics.
0.94 PXR activation is able to induce hepatocyte proliferation as is CAR or not.
0.92 CAR or PPARalpha activation induces hepatocyte proliferation and hepatocarcinogenesis in rodent models, it remains unclear whether PXR activation also shows such effects.
0.89 PXR and CAR.
0.89 PXR activation on hepatocyte proliferation and the role of PXR in the xenobiotic-induced hepatocyte proliferation mediated by CAR or PPARalpha in mice.
0.85 CAR or PPARalpha activators such as PB and fibrates are known as liver tumor promoters in rodents, our present findings suggest that PXR activators act as "enhancers" or "accelerators" in chemical carcinogenesis through enhancing the promoting abilities of CAR and PPARalpha although this possibility remains to be investigated in animal carcinogenesis studies in future.
0.82 PXR activation did not induce the hepatocyte proliferation in mice by itself whereas it enhanced the cell proliferation induced by CAR or PPARalpha.
0.69 CAR and PPARalpha, PXR activation alone had no obvious effects on the hepatocyte proliferation in mice.
0.57 PXR has such functions despite the functional similarities with CAR.
0.52 PXR Activation on the Hepatocyte Proliferation with or without CAR Activation
22503787 0.98 constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2).
0.98 CAR is activated in the hypothyroid state, and that this activation drives induction of its well known target Cyp2b10, while Cyp3a11 suppression is mainly mediated by PXR.
0.98 CAR and PXR.
0.97 CAR and PXR.
0.97 CAR-/- and also CAR-/-PXR-/- mice, and in both cases trended higher in the hypothyroid state (Fig. 4A), indicating a defect in CBZ clearance due to loss of the response of Cyp2b10, or potentially additional CAR targets.
0.97 PXR acts primarily as a direct xenobiotic receptor, CAR can be activated indirectly by diverse metabolic stresses, including type 1 diabetes, fasting and cholestasis.
0.96 PXR-mediated mechanisms, but at the same time this suppression may be compensated to some extent by CAR-mediated induction of Cyp2b10 and likely other targets.
0.95 PXR-/- hypothyroid mice, and this induction was abolished in CAR-/- mice and in and CAR-/- PXR-/- double knockouts.
0.94 CAR or PXR activation.
0.94 CAR was remarkably increased, whereas PXR mRNA remained unchanged in PTU/LI-treated hypothyroid mouse (Fig. 1B).
0.92 CAR-/-PXR-/- mice, which is consistent with previous results, means that it must depend on additional factors.
0.91 CAR-/- mice, but not in hypothyroid PXR-/- mice.
0.90 CAR and PXR in the impact of hypothyroidism on CBZ metabolism in vivo
0.89 CAR and PXR in Hypothyroid Mice
0.88 CAR-/- mice and lowest in WT and PXR-/- mice.
0.77 CAR-/- and also CAR-/-PXR-/- mice at that time point, and appeared higher in the hypothyroid than in the euthryoid mice (Fig. 4B).
0.70 CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged.
0.63 CAR or PXR, we used mouse knockout models of CAR, PXR, and both receptors.
0.59 CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil.
0.58 CAR-/- and CAR-/-PXR-/- mice failed to induce Cyp2b10 expression in response to either CBZ treatment or hypothyroid status.
0.58 CAR and PXR mediated changes of Cyp2b10 and Cyp3a11 in hypothyroid status
21498392 0.98 PXR and CAR function.
0.98 PXR and CAR in the control of CYP3A expression and more importantly, altered sub-cellular distribution of their obligatory heterodimerization partner retinoid X receptor alpha (RXRalpha).
0.98 PXR and CAR.
0.98 PXR and CAR.
0.98 PXR, CAR, and their dimerization partner RXRalpha.
0.98 PXR, CAR, VDR, PPARs, FXR, RAR, TR and LXR.
0.98 PXR and CAR seen in tumour-bearing animals.
0.98 PXR and CAR.
0.98 CAR and PXR and lead to functional impairment of other nuclear receptor regulated pathways that rely on RXRalpha heterodimerization.
0.97 CAR and PXR function may provide a partial explanation for repression of CYP3A-mediated metabolism.
0.95 CAR expression and a trend towards PXR and RXRalpha repression that did not attain statistical significance (data not shown, see Fig 5 for a summary of profiled NR expression).
0.95 PXR and CAR activation by PCN and TCPOBOP respectively, control mice exhibited substantial CYP3A4 induction as determined by both the X-Gal staining and the ONPG assays, while induction by both PCN and TCPOBOP was significantly abrogated in the tumor-bearing cohort (Fig. 2A, 2B and 3A, 3B).
0.95 CAR and PXR was impaired, as determined by CYP3A4 regulatory transgene induction in the presence of the EHS tumor.
0.81 PXR and CAR function
0.77 PXR and CAR, their functional activity in the presence of the EHS sarcoma was examined.
0.70 pregnane X receptor (PXR) and constitutive androstane receptor (CAR); energy and glucose metabolism through peroxisome proliferator-activated receptor gamma (PPARgamma); fatty acid, triglyceride and lipoprotein metabolism via PPAR alpha (alpha), delta (delta) and gamma; reverse cholesterol transport and cholesterol absorption through liver X receptor (LXR) and bile acid metabolism through farnesoid X receptor (FXR).
0.57 PXR and CAR ligands failed to induce CYP3A4 transgene expression to the same extent as in control animals.
24180433 0.98 CAR and PXR, respectively), both CAR and PXR heterodimerize with the retinoid X receptor (RXR) prior to binding of the complex to specific transcriptional enhancer response elements in DNA.
0.98 PXR activation also leads to increased expression of specific genes including xenobiotic metabolizing enzymes, many of which are also CAR-responsive.
0.98 CAR may also activate PXR, producing a combined response pattern of gene expression and functional changes.
0.98 CAR and PXR receptors, the key and associative events for PB-induced liver tumor formation appear to be predominantly CAR-dependent as such effects are absent in mice lacking CAR.
0.98 CAR, PXR and PPARalpha all heterodimerize with RXR for activation followed by binding to response elements in DNA.
0.97 constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are important nuclear receptors involved in the regulation of cellular responses from exposure to many xenobiotics and various physiological processes.
0.97 CAR, pregnane X receptor (PXR) and PPARalpha.
0.97 CAR and PXR regulate overlapping but distinct sets of genes in mouse and human liver.
0.97 PXR activators, by analogy with the MOAs for CAR activators and PPARalpha agonists, key and associative events are likely to include PXR activation, increased cell proliferation, hypertrophy, CYP3A induction and clonal expansion leading to altered foci.
0.96 CAR activation, PXR activation can also produce an induction of CYP2B enzymes, along with a greater induction of CYP3A enzymes.
0.94 CAR and PXR in establishing MOAs for rodent liver tumor development.
0.94 PXR/CAR receptor knockout mice.
0.91 PXR activators appear to produce similar effects in rodent liver to those produced by CAR activators, in that they can increase liver weight, stimulate replicative DNA synthesis and induce CYP forms.
0.85 CAR/PXR was genetically replaced with the human counterpart genes (hCAR/hPXR).
0.83 CAR activators on liver tumor formation in rodents, comparatively little information is available on the corresponding effects of compounds that specifically activate PXR.
0.74 CAR activator PB in rodents, whereas there appears to be little information on the tumorigenic effects of non-genotoxic PXR activators (e.g. PCN).
0.69 PXR activators, it is likely that the MOA for non-genotoxic activators of PXR would be similar to the MOAs established for CAR and PPARalpha activators.
18925944 0.98 CAR-regulated cell proliferation-related gene, was not significantly induced in the mouse, further supporting the hypothesis that o, p'-DDT preferentially activated PXR.
0.98 PXR-, CAR- or ER-mediated gene expression changes, o, p'-DDT induced Gadd45a, Gadd45b and Cdkn1, all of which are DNA damage-responsive genes.
0.97 PXR-specific target genes such as Apoa4 or Insig2 exhibited more pronounced induction compared to CAR-specific genes in the mouse.
0.97 Car mRNA levels decreased, possibly contributing to the preferential activation of mouse PXR.
0.97 PXR/CAR-mediated responses but also ER-mediated effects such as the induction of Cyp17a1 and Cyp7b1 in the mouse liver.
0.96 PXR/CAR-mediated responses to DDT may have a more significant role in hepatic tumor promotion.
0.96 PXR regulated based on genes known to be regulated by PXR-, CAR- or PXR/CAR.
0.96 PXR/CAR- and ER-mediated activities.
0.93 CAR-regulated genes such as Cyp1a1, Fmo5, Sult1d1 or Abcc2 were moderately induced, several PXR-target genes, including ApoA4, Ces2, Gstm2 or Insig2, exhibited strong induction.
0.93 CAR-specific targets such as Cyp1a1 (~2.2-fold), Fmo5 (~2.3-fold), Sult1d1 (~2.8-fold) and Abcc2 (~2.7-fold) showed relatively weak induction, several PXR-regulated genes were induced more strongly including ApoA4 (~5.8-fold), Ces2 (~3.4-fold), Gstm2 (~3.2-fold) or Insig2 (~5.0-fold) genes (Fig. 2D).
0.92 PXR/CAR/ER-target genes in the mouse and rat liver elicited by o, p'-DDT
0.92 PXR/CAR- and ER-mediated responses, altered steroidogenesis, oxidative stress, and DNA damage (Fig. 5).
0.87 PXR, CAR and ER in o, p'-DDT elicited effects.
0.85 Pxr- or Car-null mice.
0.75 PXR/CAR-mediated response when compared to the rat.
27709013 0.98 PXR and CAR have been defined as the master regulators of xenobiotic responses.
0.98 PXR and CAR provides the essential molecular basis by which drugs and other xenobiotic compounds regulate the expression of xenobiotic enzymes and transporters.
0.98 PXR and CAR were initially shown to regulate the expression of phase I P450 enzymes, such as the CYP3A and CYP2B enzymes.
0.98 PXR and CAR can function as master regulators of the xenobiotic response by regulating the expression of both the phase I and II drug metabolizing enzymes as well as the drug transporters.
0.98 PXR and CAR is achieved by the binding of PXR-RXR or CAR-RXR heterodimers to their binding sites in the promoter regions of drug metabolizing enzymes and transporters.
0.97 pregnane X receptor (PXR) and constitutive androstane receptor (CAR) provides the essentail molecular basis by which drugs and other xenobiotic compounds regulate the expression of xenobiotic enzymes and transporters.
0.97 PXR and CAR can regulate energy metabolism by directly regulating genes that are involved in energy metabolism, or by crosstaking with other transcriptional factors (TFs) that are implicated in energy metabolism.
0.96 PXR- and CAR-mediated regulation of enzymes and transporters can not only impact drug metabolism, but also influence many physiological and disease pathways by affecting the homeostasis of endogenous chemicals, such as bile acids, bilirubin, steroid hormones, glucose, and lipids.
0.91 pregnane X receptor (PXR) and constitutive androstane receptor (CAR) were cloned and/or established as xenobiotic receptors in 1998.
0.79 PXR and CAR are actually beyond being the "xenobiotic receptors".
0.77 PXR and CAR as xenobiotic receptors.
0.77 PXR and CAR as xenobiotic receptors.
0.64 PXR and CAR as xenobiotic receptors
0.57 PXR and CAR in drug metabolism and energy metabolism.
0.55 PXR and CAR beyond being "xenobiotic receptors"
29476044 0.98 pregnane X receptor (PXR), and constitutive androstane receptor (CAR).
0.97 PXR and CAR, species specificity in ligand binding, and the opposing effects of these receptors' activities make the net effect of xenobiotic regulation of major P450s complex.
0.97 PXR and CAR in the regulation of phase I (oxidation) and phase II (conjugation) drug metabolizing enzymes and transporters, their selectivity for different ligands including endogenous lipids and hormones, their influence on inflammatory responses, and their regulation of cholesterol, glucose, and lipid metabolism can elicit distinct differences between mice and humans.
0.97 PXR and CAR humanized mice, but not wild-type mice, displayed increased microsomal protein content, total P450 content, and P450 reductase activity in response to rifampicin treatment.
0.95 PXR and CAR regulation and CYP3A4 metabolism of ARVs, other drug metabolizing enzymes and transporters also contribute to the bioavailability and pharmacokinetics of ARVs.
0.94 PXR and CAR show significant homology in CYP3A binding sites; however, homology in their ligand-binding domains is limited.
0.92 PXR and CAR can bind multiple different ligands and their ligand specificity varies across species.
0.92 PXR-CAR-CYP3A4/7 mice, differences in the metabolite profile of drugs in combination compared with normal mice have been shown for itraconazole/cobimetinib and midazolam plus the CYP3A inhibitor clarithromycin and support our observations for the interactions of ATV and RTV.
0.89 PXR and CAR and induction of CYP3A.
0.88 PXR-CAR-CYP3A4/7 mice was shown to be reflective of the human responses.
0.87 PXR-CAR-CYP3A4/3A7) C57Bl/6 background mice treated with weekly doses of nanoATV/r showed 5-fold higher ATV plasma concentrations at study end compared with wild-type mice (unpublished data).
0.80 PXR and CAR activation and their regulation of energy metabolism may also underlie the differences in body weight in the hCYP3A-NOG and control NOG mice and the slight weight loss following treatment in NOG mice observed in the current study.
0.68 PXR, and CAR by nanoATV and nanoATV/r was greater in both male and female
0.61 PXR-CAR-CYP3A4/7 model can provide predictive values for the development of drug combinations with reduced drug-drug interactions and toxicities.
0.53 PXR, and CAR between the two strains.
18844851 0.98 PXR and CAR).
0.98 PXR, and CAR all function as RXR heterodimers and are activated by dietary lipids.
0.98 CAR, PXR, FXR, and VDR (Figure 2).
0.98 PXR and CAR ligands in the intestine.
0.98 PXR and CAR in the liver and, specifically, by VDR in the colon.
0.97 PXR, CAR), and a variety of cholesterol metabolites referred to as oxysterols (bind LXRs).
0.97 PXR and CAR are the principle modulators of detoxifying pathways involving phase I and II enzymes and phase III transporters.
0.97 PXR, CAR, and FXR play a central role in xenobiotic and bile acid metabolism.
0.97 PXR and CAR) function as sensors in the gut to protect the body from excess exposure to toxic dietary lipids.
0.94 PXR, CAR, and FXR, particularly with respect to drug interactions and first-pass metabolism; however, this system was not designed with our current pharmacopeia in mind, rather it likely evolved to protect the body from ingested toxins, toxins produced by pathogenic bacteria, or even endogenous compounds converted to toxins by commensal bacteria.
0.90 PXR, while MRP2 is also regulated by CAR.
0.88 PXR, CAR, FXR, and VDR regulate many of the same targets, there is also overlap in the chemical ligands by which they are activated.
0.85 PXR and CAR).
0.53 PXR/CAR target genes involved in drug metabolism can be found in a number of plenary reviews on the topic.
21983082 0.98 CAR, PXR, and the peroxisome proliferator-activated receptor-alpha (ppar-alpha), in addition to the environmental sensing aryl hydrocarbon receptor (AhR), regulate UGT1A1 gene expression.
0.98 PXR and CAR in regulation of the UGT1A1 gene in the GI tract after formula treatment.
0.98 PXR, or CAR.
0.97 pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play crucial roles in contributing to breast milk-induced hyperbilirubinemia and the onset of BIND and seizures, while the antioxidant protection induced by breast milk is linked to early development through suppression of the intestinal IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) signaling pathway.
0.97 PXR and CAR can lead to induction of UGT1A1 and lowering of TSB.
0.97 CAR plays a protective role against BIND by controlling expression of Mdr1a in the brain, while PXR contributes to bilirubin homeostasis by mechanisms not yet identified.
0.96 PXR and CAR activation may be involved in regulation of UGT1A1.
0.95 Car, and Pxr in the developing small intestine, dramatically lowered Cyp2b10 and Cyp3a11 were observed in the mice nursed with breast milk compared to the levels at 21 days (Supplementary Figure 2), while expression of Car and Pxr was not changed.
0.93 pregnane X receptor, constitutive androstane receptor, or nuclear factor-kappaB.
0.92 Pxr-/- and hUGT1/Car-/- mice, formula treatment effectively induced UGT1A1 along with Cyp3a11 and Cyp2b10 gene expression, indicating that induction of intestinal UGT1A1, Cyp2b10, and Cyp3a11 gene expression and reduction in TSB levels in formula-fed hUGT1 mice are not associated with either CAR or PXR expression.
0.89 Car-/-, and hUGT1/Pxr-/- mice were treated with formula for 5 days, TSB levels were reduced (Figure 3A), with none of the mice on the formula diet progressing into seizures (Figure 3B).
0.83 CAR activation, Cyp3a11 induction for PXR activation, and Cyp4a10 gene expression, which is regulated by ppar-alpha.
0.63 pregnane X receptor and constitutive androstane receptor.
0.62 CAR and PXR and Control of Hyperbilirubinemia
23330546 0.98 pregnane X receptor (PXR; NR1I2), vitamin D receptor (VDR; NR1I1), and constitutive androstane receptor (CAR; NR1I3), were shown to be activated by bile acids or bile acid metabolites.
0.98 PXR, CAR is constitutively active and is considered to be another master regulator of drug metabolism in the liver.
0.98 CAR and PXR recognize the same xenobiotic response elements in target gene promoters and thus regulate an overlapping set of target genes in xenobiotic and bile acid metabolism and detoxification (Table 1).
0.98 PXR is thought to be the major mediator of CYP3A induction in bile acid hydroxylation, CAR is thought to play a central role in inducing LCA sulfation, because the resistance of CAR transgenic mice to LCA toxicity was associated with increased LCA sulfation independent of CYP3A induction.
0.97 PXR knockout (KO) mice were administered CA, they were protected from bile acid toxicity and CAR target genes Ctp2b, Cyp3a, Mrp2, Ugt1a1, and Gsta were induced, suggesting that FXR, PXR, and CAR protect against hepatic bile acid toxicity in a complementary manner.
0.97 CAR had a higher degree of liver injury than wild-type (WT) mice during LCA- or BDL-induced cholestasis, and such liver damage was aggravated in CAR/PXR double KO mice, suggesting that PXR and CAR may play overlapping, but also complementary, roles in bile acid detoxification.
0.97 PXR and CAR are also attractive drug targets for treating cholestasis, based on their key function in the activation of the bile acid detoxification network.
0.96 PXR, CAR, and VDR all play roles in the three phases of drug and bile acid metabolism in the liver and intestine.
0.93 PXR, CAR, and VDR in regulation of bile acid metabolism and toxicity
0.92 CAR and PXR also affect glucose and energy metabolism.
0.92 PXR, CAR, and VDR are promising therapeutic targets for the treatment of liver and metabolic diseases.
0.83 PXR, VDR, and CAR target genes identified in bile acid metabolism are shown in Table 1.
0.69 PXR, VDR, and CAR in regulation of drug and bile acid metabolism.
31815118 0.98 PXR is considered promiscuous because it binds a variety of bile acids, steroids and xenobiotics in mammals, including a large number of endocrine disrupting chemicals, providing circumstantial evidence that the PXR and its close relative, CAR, are protectors of the endocrine system.
0.97 PXR, CAR, MTF, Nrf2, NF-kappaB, and AP-1.
0.97 CAR and PXR, and in turn increased metabolism of atrazine.
0.97 PXR and CAR by steroids, steroid precursors, and bile acids, and of course numerous xenobiotic chemicals that activate all of the transcription factors mentioned previously.
0.96 CAR and PXR's role in the induction of crucial phase I-III detoxication proteins, it is not surprising that CAR and PXR are associated with protection from anthropogenic pollutants and endobiotics.
0.96 CAR-null and PXR-null mice are also less sensitive to acetaminophen, and activation of these receptors and subsequent CYP induction increases NAPQI production and toxicity.
0.95 CAR or PXR activation increases the metabolism, detoxication, and clearance of bile acids.
0.95 CAR and PXR are activated by specific xenobiotics (X).
0.92 PXR or CAR activation increases metabolic activation and the toxicity of the chemical.
0.89 pregnane X-receptor (PXR), its relative the constitutive androstane receptor (CAR), and their invertebrate ortholog, HR96.
0.88 CAR and PXR activation, respectively.
0.74 CAR and PXR in xenobiotic metabolism.
0.58 PXR (and to a lesser extent CAR) has provided crucial information on drug-drug interactions and therefore saved lives.
20005886 0.98 CAR/PXR regulation.
0.98 CAR/PXR-mediated insulin induced genes (Insig1 and Insig2) also repress Srebf1, thereby lowering hepatic fatty acids.
0.97 pregnane X receptor (CAR/PXR) regulated genes including Cyp2b10, Cyp3a11, Ces2, Insig2 and Abcc3 were dose-dependently induced by PCB153.
0.95 CAR/PXR regulation.
0.92 PXR/CAR response elements in the promoter region (-10,000 bp relative to the [TSS] together with the 5' UTR) of responsive genes identified from the microarray analysis (Table 3).
0.91 CAR/PXR regulated genes, such as Ces2, Cyp2b10, Fmo5, Fasn, Insig2, Abcc3 and Gsta2 (Table 3).
0.91 CAR/PXR-mediated hepatic hypertrophy.
0.91 CAR/PXR regulated genes, Cyp2b10, Cyp3a11, Cyp2c55 and Gadd45b, in (A) time course and (B) dose-response studies.
0.89 CAR/PXR-mediated regulation.
0.86 CAR/PXR responsive genes.
0.85 CAR/PXR-regulated genes Cyp2b10, Cyp3a11 and Gadd45b, as well as Cyp2c55 (48-fold) by PCB153 and TCDD was also confirmed (Fig.5A-C).
0.84 constitutive androstane receptor (CAR)/ pregnane X receptor (PXR).
18789671 0.98 CAR (constitutive androstane receptor) and/or PXR (pregnane x receptor).
0.98 PXR and CAR regulate MDR1 expression.
0.98 PXR and CAR, the aryl hydrocarbon receptor (AhR) also modulates the inducible expression of CYP genes, the most highly characterized of which is the modulation of CYP1A and CYP1B subfamilies.
0.91 PXR and CAR (Table 1).
0.90 CAR or PXR does not require an increase in the expression of these receptors.
0.89 CAR and PXR, although our RT-qPCR data indicate that hepatic gene expression of CAR and PXR was unchanged by alpha-tocopherol supplementation.
0.89 CAR or PXR genes are up-regulated.
0.88 PXR and CAR have overlapping specificity with respect to hepatic up-regulation of CYP3A, CYP2B and CYP2C subfamilies, Por, GST mu, MDR1 and Mdr1a.
0.87 Car gene expression increased 1.8-fold and Pxr gene expression increased 1.6-fold in ++E compared with E mice (Table 1, P < 0.05).
0.84 PXR and/or CAR.
0.56 Car (1.1 +- 0.02) and Pxr (1.3 +- 0.13) was not significantly different in ++E mice compared to E mice (Figure 3).
22371261 0.98 PXR and CAR have been classified as steroid and xenobiotic sensors, so it can be anticipated that significant fluctuations in the pregnancy hormones will modulate transcriptional control of target genes such as those involved in xenobiotic or drug metabolism.
0.98 Car-/- mice during pregnancy, displays reduced expression at GD16 in hUGT1*1/Pxr-/- mice.
0.98 PXR and CAR control the induction of all these genes have not been determined, although PXR and CAR-responsive elements have been shown to play an important role in PXR/CAR binding and induction of the UGT1A1 gene.
0.98 Car-/- mice but greatly diminished in hUGT1/Pxr-/- mice, suggesting that PXR participates in a global fashion to regulate the UGT1 locus during fetal development.
0.98 PXR/CAR appear to be necessary for induction of UGT1A9 during pregnancy, there may be crosstalk occurring between the two xenobiotic receptors to facilitate regulation of the UGT1A9 gene.
0.97 pregnane X receptor (PXR) and constitutive androstane receptor (CAR), may underlie the induction process.
0.97 pregnane X receptor (PXR) and the constitutive androstane receptor (CAR).
0.97 PXR or CAR leads to induction of UGT1A1, -1A3, -1A4, -1A6, and -1A9.
0.95 PXR and 17beta-estradiol has been shown to activate CAR.
0.91 PXR and CAR toward induction of the UGT1 locus during pregnancy.
0.77 PXR and CAR during pregnancy was investigated using reverse genetics to examine induction of the UGT1A genes in xenobiotic receptor-defective mice.
28181583 0.98 CAR and PXR.
0.98 PXR and/or CAR activities (Fig. 2d,e).
0.98 Pxr and Car are expressed within the testis.
0.97 PXR and CAR signaling pathways are modulated in a tissue dependent manner in response to altered BA homeostasis
0.97 Pregnane-X-Receptor (PXR; NR1I2); whereas the transcritpional activity of the Constitutive Androstan Receptor (CAR; NR1I3) is repressed by several bile acids, among which CA, tauro-CA and conjugated form of DCA.
0.97 PXR agonists, and mutation of Hsd3b7 was associated with the production of intermediates defined as CAR inverse agonists.
0.95 PXR and/or CAR activities.
0.95 PXR and/or CAR activities.
0.94 PXR and/or CAR signaling pathways should be involved in the phenotype observed in Fxralpha-/- males fed BA-diet.
0.93 PXR, CAR and/or FXRalpha in different specific cell types of the targeted organs.
0.89 CAR specific versus PXR.
18778245 0.98 CAR (constitutive androstane receptor) and, to a lesser degree, PXR (pregnane X receptor).
0.98 CAR, PXR, LXR (liver X receptor) and HNF4alpha (hepatocyte nuclear factor 4alpha).
0.98 CAR (and possibly PXR), leading to P450 induction and liver growth through the activation of other downstream growth/transcription factors.
0.98 CAR (and possibly PXR), leading to P450 induction and liver growth.
0.97 PXR (pregnane X receptor) and CAR (constitutive androstane receptor), which have the capacity to bind drugs and exogenous chemicals, resulting in transcriptional activation of genes that mediate their detoxification.
0.97 CAR-dependent manner and possibly a PXR-dependent manner, as suggested by the opposing effects on this protein's expression observed in Car-/- and Pxr-/-/Car-/-/HRN mice.
0.95 CAR and PXR, which have been intimately linked to the regulation of CYP2B and CYP3A proteins in response to both exogenous and endogenous inducing agents, and PXR has been linked to triacylglycerol homoeostasis.
0.95 CAR, PXR and protein stabilization.
0.94 PXR and CAR.
0.72 CAR and PXR on an HRN background resulted in an increase in non-fasting plasma total cholesterol level that was not significantly different from control (Porlox/lox) mice.
25949234 0.98 CAR to respond to environmentally-relevant chemicals allows CAR, in concert with other transcription factors (e.g., pregnane X receptor (PXR, NR1I2) and aryl hydrocarbon receptor (AhR)), to induce gene expression of enzymes and transporters that metabolize and remove potentially toxic xenobiotics from the liver.
0.98 PXR and part of a PXR biomarker signature (Oshida et al., in preparation), as well as Cyp3a11, a prototypical marker gene for PXR, were activated by propiconazole and triadimefon in wild-type and CAR-null mice, consistent with a CAR-independent mechanism.
0.97 PXR activators (but not PPARalpha activators) require their receptors for CAR activation, leads to the hypothesis that the activation of CAR requires a factor(s) that is dependent on prior activation of AhR or PXR.
0.95 CAR at least partly through a PXR-dependent mechanism (Figure 6).
0.94 CAR by PXR activators was partially or completely PXR-dependent.
0.92 CAR was activated by 1) activators of the aryl hydrocarbon receptor (AhR) in wild-type but not AhR-null mice, 2) pregnane X receptor (PXR) activators in wild-type and to lesser extents in PXR-null mice, and 3) activators of PPARalpha in wild-type and PPARalpha-null mice.
0.91 CAR and PXR, the effects of PXR activator exposure on CAR activation were examined.
0.85 PXR-null mice, the significance of the activation of CAR was diminished but not abolished compared to wild-type mice.
0.83 CAR and other signaling pathways: activation of CAR by PXR activators
0.68 CAR by PXR activators is diminished or abolished in PXR-null mice (from this study and GSE23780).
19041682 0.98 CAR or PXR with RXR and subsequent interaction with the phenobarbital responsive enhancer module (PBREM) or xenobiotic responsive enhancer module (XREM) induces the expression of classical biomarkers such as Cyp2b10 (CAR) and Cyp3a11 (PXR) as well as other CYP genes involved in detoxification.
0.98 CAR-null mice, suggesting the activation of PXR (Fig. 4A) similar to that observed for Cyp3a11.
0.98 CAR and the glucocorticoid receptor (GR), which controls the expression of PXR.
0.98 CAR-null females treated with NP but not TC showed a significant albeit diminished decrease in paralysis time compared to untreated CAR-null females, suggesting activation of PXR and induction of Cyp3a subfamily members in a CAR-independent fashion as observed by QPCR (Fig. Fig. 3c, 4a,c).
0.97 CAR and its relative, the pregnane X receptor (PXR), cross talk by sharing response elements and showing overlapping affinities for some ligands; providing each other a backup system for responding to toxicants, but also increasing nuclear receptor interactions and making it difficult to interpret some data.
0.97 CAR or PXR.
0.97 CAR-null mice, suggesting activation of PXR by NP.
0.97 CAR-null mice show a small but significant decrease in paralysis time, suggesting activation by PXR in addition to CAR (Table 1).
0.97 CAR > PXR.
19845433 0.98 PXR and CAR have been shown to be involved in regulation of UGT1A1 gene expression both in vitro and in vivo.
0.98 CAR, and probably PXR and PPAR-alpha, up-regulate UGT1A4 expression in vivo.
0.97 PXR is evolutionarily related to CAR (40% homology) and is thought to play a role in regulation of metabolism, transport and excretion, perhaps as a protective mechanism in cholestasis.
0.97 PXR and CAR may function as modulators of hUGT1A4 in the liver and that murine PXR and CAR bind to the human response elements in the regulatory region of the hUGT1A4 gene.
0.96 PXR, CAR, PPAR-alpha and AhR increased the formation of LTGG as a result of 72-h pretreatment.
0.96 PXR and CAR in up-regulation of UGT1A4 enzyme in the liver.
0.94 CAR inducers, though it is speculated that it may activate PXR at higher concentrations.
0.91 pregnane X receptor (PXR), CAR is found in low levels in the liver, has a limited tissue distribution, and is activated by fewer xenobiotics as compared with PXR.
0.76 pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor (PPAR) activators on LTG glucuronidation in vivo and in vitro.
27635169 0.98 pregnane x receptor, constitutive androstane receptor, and farnesoid x receptor) in an RXRalpha dependent manner to induce hepatocyte proliferation, providing a link between RA and its proliferative role.
0.98 PXR, CAR, and FXR, RA can exert its mitogenic effect in the liver.
0.98 PXR/CAR double knockout mice.
0.98 PXR, CAR, and FXR pathways, which could potentially mediate its mitogenic effect (illustrated in Figure 2).
0.98 pregnane x receptor (PXR), constitutive androstane receptor (CAR), farnesoid x receptor (FXR) and their downstream pathways to regulate hepatocyte proliferation.
0.97 PXR and RXRalpha/CAR, and therefore RXRalpha is the permissive partner of PXR and CAR.
0.97 PXR/CAR and PPARalpha.
0.95 CAR, PXR, as well as others.
0.85 CAR, PXR, and FXR causes hepatomegaly or liver cancer.
30396153 0.98 CAR are important hepatocyte regulators with similar binding sites: homodimeric HNF4alpha and RXR heterodimeric partners PPARalpha, FXR, LXRalpha/beta, PXR, and THRalpha/beta.
0.96 PXR, like CAR, is a drug and xenobiotic receptor.
0.96 CAR inhibition of genes stimulated by PXR or THR linked to separate enhancers.
0.96 CAR and HNF4alpha constitutively mediate this LBD-driven process; PPAR, FXR, LXR, PXR, and THR require an activating ligand; and RXR is usually considered a passive partner.
0.94 CAR, HNF4, RXR, FXR, LXR, PPAR, PXR, and THR peaks, overlapping in different combinations (Figure 6C).
0.92 PXR (and CAR), however, activating ligands are normally present in the liver.
0.91 CAR binding on HNF4+ and HNF4- sites that overlap with RXR, FXR, LXR, PXR, and THR (arrows, 66 and 2.4 kb from the Mlxipl TSS).
0.85 PXR, and THR are more ambiguous, but coexpression of these NRs with CAR in the same hepatocytes is well known.
0.78 PXR distinctively showed a cooperative relationship with CAR, since TCPOBOP stimulated acetylation of PXR-positive more than PXR-negative peaks.
18940178 0.98 PXR, CAR and RXRalpha).
0.98 PXR and CAR, Cyp3a11 and Mrp2 were moderately reduced by LTA, along with ~50% reduction of PXR RNA and nuclear protein levels of RXRalpha.
0.98 PXR and CAR heterodimerize with the central nuclear receptor, RXRalpha to bind to conserved sequences in the promoter regions of DME and transporter genes resulting in activation of these genes.
0.97 pregnane X receptor (PXR), constitutive androstane receptor (CAR) and retinoid X receptor (RXRalpha).
0.97 CAR gene expression in inflammation has also been attributed to the disruption of GR-mediated transactivation of the CAR gene by NF-kappaB. Recent work has demonstrated that NF-kappaB can interact with PXR-RXR complex, leading to the suppression of Cyp3a4 gene expression by LPS.
0.97 PXR and CAR, while Ugt1a1 is known to be primarily regulated by PXR in mouse liver.
0.96 CAR target gene, and Cyp2a4 and Sultn are known to be regulated only by CAR, and not PXR in mouse liver.
0.94 PXR, CAR and RXRalpha, the role of these NRs in regulation of LTA-mediated alterations of hepatic gene expression can be best addressed by transgenic mice.
19489075 0.98 CAR or PXR targets.
0.97 CAR and PXR have emerged as primary mediators of such inductive effects, and their species-specific responses to particular xenobiotic and endobiotic inducers have been well characterized.
0.96 Car-/- mice, but is unaffected by the loss of PXR.
0.95 CAR or PXR activation could account for the induction of drug metabolism in Type I diabetes.
0.94 CAR and its close relative PXR are major regulators of drug metabolism.
0.94 PXR appears to act primarily in xenobiotic induction of drug metabolism, while CAR may be more important in response to endogenous stimuli.
0.89 CAR and PXR in this process.
0.79 CAR activation maintains in diabetic hCAR mice, NOD mice and PXR-/- mice
26215100 0.98 PXR, CAR and AhR regulate an overlapping set of xenobiotic metabolism genes, activation or suppression of one transcription factor likely has effects on the others.
0.98 CAR and PXR activators, albeit at high dose levels (Fig. 5C and D).
0.94 CAR and PXR activator exposure at high doses leading to suppression of AhR.
0.90 CAR)-dependent manner and pregnenolone-16alpha-carbonitrile in a pregnane x receptor (PXR)-dependent manner.
0.86 CAR or PXR activators suppressed AhR. TCPOBOP suppressed AhR in wild-type but not CAR-null mice; phenobarbital also suppressed AhR that approached significance in wild-type mice (Fig. 5C, left panel) (from GSE40120).
0.86 CAR and/or PXR activation leads to suppression of AhR. Suppression could come about through competition for essential cofactors or possibly through the regulation of endogenous activators of AhR.
0.75 CAR, Nrf2, PPARalpha, PXR and RXR.
0.68 CAR and PXR activators
27773686 0.98 constitutive androstane receptor (CAR), liver X receptor (LXR), and pregnane X receptor (PXR) also heterodimerize with the RXR and regulate transcription of genes involved in bile acid and lipid homeostasis, complicating interpretation of the results generated with FXR.
0.96 CAR, LXRalpha, and PXR) that also heterodimerize with the RXR and coordinate with FXR to regulate subsets of downstream effectors and signaling pathways involved in energy and xenobiotic metabolism.
0.96 CAR, LXRalpha, and PXR.
0.95 CAR and LXRalpha, but partially increased the expression of the PXR-luc reporter gene.
0.94 CAR, LXRalpha, and PXR.
0.86 CAR, LXRalpha, and PXR.
0.77 constitutive androstane receptor (CAR), liver X receptor alpha (LXRalpha), or pregnane X receptor (PXR).
0.68 CAR, LXRalpha, and PXR.
20070245 0.98 CAR is a sister xenobiotic receptor of PXR that has also been shown to regulate the expression of drug metabolizing enzymes including UGTs.
0.98 PXR and CAR function as xenobiotic receptors that regulate the expression of genes encoding the Phase I and Phase II drug metabolizing enzymes and transporters.
0.98 PXR and CAR to their response elements found within the target gene promoters.
0.98 PXR and CAR are tissue-specific transcription factors that play an important role in the regulation of UGTs, and the NR-mediated UGT regulation may have contributed to the tissue-specific expression pattern of UGTs.
0.92 PXR has both negative and positive roles in bilirubin clearance and that this dual role of PXR is achieved, at least in part, by cross-talking with CAR.
0.76 CAR knockout and the double knockout mice showed similar sensitivity as the wild-type mice, the PXR knockout mice exhibited a surprisingly complete resistance to hyperbilirubinemia.
0.67 PXR and CAR was examined using PXR and CAR single or double knockout mice, it was found that the loss of PXR and/or CAR did not significantly alter the basal level of serum bilirubin.
21898498 0.98 CAR, PXR, RXRalpha and FXR, play pivotal roles in APAP metabolism and toxicity.
0.98 CAR and PXR, protected mice from APAP toxicity primarily by regulating the expression of Gst enzymes.
0.97 pregnane X receptor (PXR), constitutive androstane receptor (CAR), and retinoid X receptor alpha (RXRalpha).
0.93 CAR or PXR was shown to heighten APAP hepatotoxicity.
0.92 CAR and PXR, activation of LXR was beneficial in relieving APAP hepatotoxicity.
0.88 CAR/PXR-activated mice, was absent in LXR Tg mice.
0.76 CAR/PXR-activated mice.
28350814 0.98 CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members.
0.98 CAR and PXR crosstalk and there is weak but insignificant induction of several other CAR/PXR regulated CYPs including Cyp2b10, Cyp2c29, and Cyp2c40 (Table 2) with increased protein levels of CYP2B (Fig 4).
0.97 CAR, PXR, and potentially other nuclear receptors/transcription factors that regulate CYP expression.
0.96 PXR and potentially a drop in CAR activity.
0.95 CAR-null mice, suggesting either a drop in CAR activity in Cyp3a-null mice or more likely an increase in PXR activity.
0.91 CAR-null mice and suppressed in female CAR/PXR-null mice.
0.83 CAR expression with HNF4alpha > CAR > PXR regulation of constitutive Cyp expression.
28785378 0.98 CAR, PXR, Nrf2, and PPARalpha downstream proteins, as well as CALR and CANX was detected, likely being a result of adaptation to high levels of 8-OHdG in the DNA (Table 2).
0.98 CAR and PXR were significantly activated in the surrounding liver tissue of both Ogg1-/- and Ogg1+/+ PB-treated animals.
0.98 CAR-, PXR-, Nrf2-, and PPARalpha-related proteins, CALR, and CANX.
0.97 CAR- and PXR-related proteins participated in the regulation of LPS/RXR, and xenobiotic metabolism were significantly increased in the livers of both PB-treated Ogg1-/- and Ogg1+/+ animals.
0.97 CAR- and PXR-dependent induction of phase I and II metabolic enzymes in both Ogg1 homozygous mutant and wild-type mice, but insufficient, or no Nrf2 activation in the Ogg1-/- livers and HCCs, respectively, pointing out that nonrepaired 8-OHdG and uncontrolled accumulation and damage from the reactive oxygen species in Ogg1-/- liver tissue could become the reason of progression of hepatic adenoma to carcinoma (Figure 5).
0.96 CAR and PXR downstream enzymes involved in xenobiotic metabolism including CYP2B10, CYP3A11, CYP2A5, CYP1A2, CYP2C54, cytochrome b5 type A (CYB5A), carboxylesterase 1 (CES1), POR, GST alpha 3 (GSTA3) and alpha 4 (GSTA4), GST mu 1 (GSTM1), GST mu 3 (GSTM3), GST mu 5 (GSTM5), UDP-glucose 6-dehydrogenase (UGDH), and paraoxonase 1 (PON1) was demonstrated by proteome analysis.
0.96 CAR and PXR downstream proteins, 4-hydroxyphenylpyruvate dioxygenase (HPD), glycine N-methyltransferase (GNMT), glycine-N-acyltransferase (GLYAT), paraoxonase 1 (PON1), and urea cycle enzymes were also overexpressed in PB-treated Ogg1-/- HCCs, but not in Ogg1+/+ HCAs (Table 2).
19742318 0.98 CAR and PXR, which control the metabolism of drugs.
0.98 CAR and PXR.
0.97 Constitutive Active/Androstane Receptor (CAR), and the Pregnane X receptor (PXR).
0.97 CAR and PXR are not involved in the upregulation of xenobiotic metabolism (except for Cyp2b10 and Cyp2C38), but the effect was attributed to increased levels of bile acids and signaling through FXR.
0.96 CAR and PXR induce Insig-1 by CAR and PXR which may explain the negative effects of some drugs on hepatic lipid levels.
0.95 CAR and PXR also regulate homeostasis of cholesterol, bile acids, sterols, lipids, heme and other endogenous hydrophobic molecules.
21354151 0.98 CAR is a sister receptor of PXR that has also been implicated in bile acid detoxification .
0.96 PXR and CAR on lithogenesis, although paradoxical, is consistent with the notion that these two receptors have overlapping, yet distinct, spectrums of target genes and physiological functions.
0.95 CAR-/- mice, we found that the majority of lithogenic diet-responsive hepatic and intestinal gene regulation observed in PXR-/- mice was absent in CAR-/- mice.
0.84 PXR, because loss of CAR, a sister xenobiotic receptor of PXR, had little effect on CGD susceptibility (Supplementary Fig. 4).
0.83 CAR and PXR share many of their target genes and pathophysiological functions.
0.58 PXR, because loss of CAR had little effect on CGD.
21495846 0.98 PXR, CAR, and VDR in hepatoprotection from BA toxicity through regulation of genes involved in BA detoxification, including hydroxylation, export, and sulfation.
0.98 CAR and PXR.
0.98 PXR and CAR can suppress lipogenesis through activation of Insig-1, an endoplasmic reticulum-associated membrane protein that prevents proteolytic activation of SREBP.
0.97 pregnane X receptor (PXR), constitutive androstane receptor (CAR), and the vitamin D receptor (VDR), which act together with the heterologous binding partner retinoid X receptor (RXR) to transactivate target gene expression.
0.97 CAR, impacts several metabolic pathways and is activated by many of the same ligands as PXR.
0.67 PXR and CAR also appear to influence glucose metabolism and the fasting response.
23240054 0.98 pregnane X receptor (PXR; NR1I2) and constitutive androstane receptor (CAR; NR1I3), both of which play a role in the regulation of xenobiotic metabolism.
0.98 CAR, comparison of CAR-null, PXR-null and PXR/CAR-double knockout mice shows that CAR plays a role in the elimination of toxic bile acids through a xenobiotic metabolic pathway.
0.97 CAR and PXR bind to response elements with overlapping specificity, and coordinately regulate xenobiotic metabolism.
0.97 PXR and CAR, and BDL has been shown to increase Cyp3a11 expression.
0.90 pregnane X receptor and constitutive androstane receptor, an understanding of the role of VDR in xenobiotic metabolism remains limited.
0.86 PXR and CAR, however, our understanding of the role of VDR in xenobiotic metabolism remains limited.
23949303 0.98 Constitutive androstane receptor (Car), Farnesoid x receptor (Fxr), Pregnane x receptor (Pxr), and Nuclear factor E2-related factor 2 (Nrf2) are transcription factors previously described to regulate transporter expression in liver.
0.97 Car, Fxr, Pxr, and Nrf2 target genes were regulated similarly in lean livers.
0.97 Car, Fxr, Hnf4alpha, Pxr pathways.
0.97 Pxr binding activity, and increased Car pathway activity.
0.95 Car, Fxr, Pxr, and.
0.91 Car, Pxr, or Fxr activity.
26179144 0.98 CAR, PXR and Nrf2 regulates not only Ces mRNA expression, but also isoform-specific activity.
0.97 PXR and CAR agonists pregnenolone-16a-carbonitrile (PCN) and 1,4-bis-[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), respectively.
0.97 CAR and PXR by demonstrating induction of Ces at the mRNA level.
0.96 CAR activator 1,4-bis-[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and PXR ligand pregnenolone-16a-carbonitrile (PCN) increased Ces mRNA expression of various Ces2 isoforms, whereas the Nrf2 activator butylated hydroxyanisole (BHA) primarily reduced Ces3a mRNA expression and induced Ces1g mRNA.
0.94 CAR, PXR and Nrf2.
0.89 constitutive androstane receptor (CAR), pregnane X receptor (PXR) and nuclear factor-E2-related protein (Nrf2) to mice.
30761355 0.98 PXR and CAR [ - ], although negative regulation of SULT2A1 by FXR has been reported in mice (Table 1).
0.98 CAR activation leads to the overexpression of MRP4 (basolateral export of sulfated sterols) and MRP2 (canalicular export of glucuronidated bile acids) in mice, while activated PXR upregulates the murine basolateral exporters MRP3 and MRP4, which transport sulfate- and/or glucuronite-conjugated bile acids out of hepatocytes .
0.98 PXR, and CAR, as well as the bile acids that activate these receptors and/or Abcc2 directly (Table 1).
0.97 pregnane X receptor (PXR, section 3.3.3) and constitutively active/andostane receptor (CAR, section 3.3.4) play important roles in activating numerous bile acid detoxification mechanisms.
0.96 PXR (section 3.3.3), CAR (section 3.3.4), and VDR.
0.92 PXR, CAR, and LRH-1 in PHx-induced liver regeneration could help with understanding the role of bile acids in liver regeneration.
23349477 0.98 CAR is a sister receptor of PXR that shares many functions in xenobiotic regulation.
0.97 pregnane X receptor (PXR), along with its sister receptor constitutive androstane receptor (CAR), was initially characterized as a xenobiotic receptor that regulates drug metabolism.
0.63 CAR and PXR appeared to have opposite effects on metabolic disease.
0.58 PXR and CAR as sister receptors of overlapping, yet distinct, functions.
0.51 CAR ablation is opposite to the antidiabetic effect of PXR oblation.
19433268 0.98 CAR and the pregnane X receptor (PXR) can protect the liver against bile acid-induced cholestasis via up-regulation of bile acid metabolizing genes such as Cyp3A and Sult2A.
0.97 CAR or PXR, prior to insult with LCA, protects against the hepatotoxic effects of accumulating bile acids.
0.93 CAR in the observed hepatoprotection is clearly supported by the increased liver injury in the absence of CAR and the observation that even the PXR activator PCN is not hepatoprotective in the absence of CAR.
0.86 CAR (PB, TC) and PXR (PCN) the tissue damage caused by LCA is absent, with liver sections similar in appearance to vehicle controls.
21335546 0.98 pregnane X receptor (PXR/NR1I2), and constitutive androstane receptor (CAR/NR1I3); each of which is capable of inducing the expression of broad-specificity hepatic and intestinal phase I enzymes (CYP2C9 and CYP3A4) that play major roles in metabolic detoxification of xenobiotics and endobiotics such as bile acids.
0.98 CAR and PXR.
0.97 PXR, and CAR protect against hepatic bile acid toxicity in a complementary manner and nuclear receptors can be modulated by synthetic drugs and natural products.
0.95 PXR, and CAR perform overlapping functions in altering bile acid metabolism and elimination.
24801167 0.98 CAR and PXR.
0.97 constitutive androstane receptor (CAR), farnesoid X receptor (FXR), liver X receptor (LXR), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others, regulate energy homeostasis, the formation and excretion of bile acids, and detoxification of xenobiotics.
0.97 CAR, farnesoid X receptor (FXR), liver X receptor-alpha (LXRalpha), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others.
0.81 PXR, also called steroid X receptor (SXR), like CAR, is a xenobiotic sensor.
27434302 0.98 pregnane X receptor (PXR) and the constitutive androstane receptor (CAR).
0.98 CAR, exceeding the amount of PXR regulated P450 enzymes.
0.98 PXR target gene, all of these P450 isoforms are regulated by CAR.
0.87 PXR target gene (7), it is likely that PXR instead of CAR is responsible for this response.
20099825 0.98 CAR and PXR thorough PBREM and the xenobiotic-responsive enhancer module, the response of the cyp2b10 gene in a CAR KO background is indicative of PXR responsiveness to these flavonoids.
0.97 CAR and PXR act to protect the body by up-regulating phase I, II and III detoxifying genes.
0.58 CAR belongs to the nuclear receptor subfamily (NR1I) along with its relative the pregnane X receptor (PXR).
20854191 0.98 PXR, CAR and PPARalpha regulating liver functions.
0.97 pregnane X receptor (PXR), and constitutive androstane receptors (CAR)], as well as epigenetic factors recognized recently.
0.96 CAR and PXR) were changed.
22554043 0.98 PXR and CAR primarily regulate the expression of the phase I DMEs CYPs, recent mouse model studies have revealed that PXR and CAR may also regulate non-CYP genes involved in phase I drug metabolism, such as CES1/2 and Aldo-keto reductases.
0.90 PXR and CAR activator, the antiepileptic drug phenobarbital, can cause acetaminophen-induced hepatotoxicity in a mouse model.
0.75 PXR and CAR have been generated.
26586440 0.98 constitutive androstane receptor (CAR) and pregnane X receptor (PXR), best known as xenobiotic sensors, regulate bile acid detoxification by stimulating the expression of hepatic genes responsible for the modification, conjugation, and transport of bile acids.
0.98 CAR, and PXR, have been reported as important regulators of cholesterol and bile acid metabolism in the liver.
0.97 PXR, LXR, and FXR remained largely unaltered by Baf60a deficiency, the expression of CAR was markedly lower in BaLKO livers than control (Figure 2C).
27240521 0.98 PXR, the CAR cognate xenobiotic receptor.
0.98 PXR, a cognate CAR receptor, is associated with gastro-intestinal barrier permeability and reduced tight junction protein levels.
0.95 Pregnane X Receptor (NR1I2) and the Constitutive Androstane Receptor (CAR, NR1I3), are sensors of toxic byproducts.
29159133 0.98 CAR-associated transcript (494-fold higher than unexposed WT animals) consistent with direct activation of this nuclear receptor, but no significant increase in the transcripts associated with AhR, PXR, or PPAR-alpha (Table 6).
0.97 CAR/PXR receptors.
0.95 CAR signaling (Cyp2b10), PXR signaling (Cyp3a11), and PPAR-alpha signaling (Cyp4a10).
29734330 0.98 CAR, PXR and AHR.
0.98 Pregnane X Receptor (PXR, Nr1i2) and the Constitutive Androstane Receptor (CAR, Nr1i3) represent the two key nuclear receptors controlling the expression of enzymes and transporters involved in bile detoxification and excretion in hepatocytes.
0.98 CAR has been shown to have a fundamental protective role in the response to LCA in vivo since CAR-KO mice have more severe defects in LCA detoxification compared to PXR-KO mice and CAR activation in transgenic mice confers resistance to the hepatotoxicity of LCA.
30910785 0.98 CAR/PXR models, that compounds such as RIF, CITCO, TCPOBOP, and dexamethasone exhibit profound species differences in the activation of these transcription factors.
0.97 constitutive androstane receptor (CAR) and the pregnane X receptor (PXR).
0.94 CAR and PXR, are complex particularly when multiple drug combinations are being used.
26363009 0.98 PXR and CAR, by exogenous ligands, endogenous ligands, or upstream signalling pathways known to increase its levels.
0.96 PXR, but not of the closely related constitutive androstane receptor (CAR), profoundly reduced circulating levels of vemurafenib in humanized mice.
30336042 0.98 PXR and CAR, inhibiting the receptors' transcriptional activities through prevention of their respective interaction with nuclear coregulators.
0.98 CAR involve cross-talk with other nuclear receptors, including PXR, LXR, FXR, PPAR and TH, as well as the interactions with insulin- or glucagon-responsive transcription factors such as HNF4alpha, C/EBPalpha, PGC-1, and FOXO1.
20727377 0.98 PXR and CAR in the liver and intestine.
24721462 0.98 CAR, a sister xenobiotic hormone receptor of PXR which is not expressed in adipose tissue, is also able to transduce its metabolic effects in both WAT and BAT.
28743453 0.98 PXR cognate receptor CAR was associated with discrete signs of neuro-vascular inflammation in the adult mouse brain.
29888801 0.98 PXR is reported to potentiate TCPOBOP/CAR-mediated hepatocyte proliferation.
30048004 0.98 PXR is a direct activator of growth arrest and DNA damage-inducible 45beta (GADD45B), which was reported to be associated with CAR-induced liver hypertrophy.
21376070 0.97 CAR-null mice; the induction of several other Cyps including Cyp2a4 and Cyp3a11 was observed in CAR-null female mice suggesting NP activation of PXR.
0.97 CAR and PXR work together to regulate NP-mediated CYP induction.
0.97 CAR and PXR appear to work together to increase NP-mediated CYP induction.
0.94 CAR and we hypothesized that some CYP induction, such as the induction of Cyp2b, would be preserved in PXR-null mice due to CAR activation.
0.92 CAR and PXR, Cyp induction may be mediated by either CAR or PXR activation (especially Cyp2b).
0.86 CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating NP is also a CAR activator.
24675475 0.97 CAR-null and PXR-null mice treated with model CAR or PXR activators also reported that Gadd45(3 expression is CAR-mediated and strongly induced by a model CAR activator.
0.97 CAR/PXR-mediated enzyme induction.
0.97 CAR/PXR signaling, namely Cyp induction and cell cycle/proliferation (Table 3).
0.91 CAR/PXR activation.
0.80 CAR/PXR-responsive genes included large increases in expression of Cyp2b10, Gadd45beta and Cyp2c65.
0.73 CAR/PXR activation.
23926955 0.97 constitutive androstane receptor (CAR), pregnane X receptor (PXR), and peroxisome proliferator-activated receptor-a (PPARalpha) are transcription factors that mediate xenobiotic inductionof Cyp genes.
0.96 CAR is responsible for the regulation of the Cyp2 family (e.g., Cyp2b10), PXR for the Cyp3 family (e.g., Cyp3a11, Cyp3a25), and PPARalpha for the Cyp4 family (Cyp4a10, Cyp4a14).
0.95 CAR, PXR, PPARalpha, and FXR.
0.91 CAR and CAR-regulated Cyp2b10, PXR and PXR-regulated Cyp3a11 and Cyp3a25, PPARalpha and PPARalpha-regulated Cyp4a10 and Cyp4a14, and FXR and FXR-regulated Cyp7a1 and Cyp27a1.
29738703 0.97 constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity.
0.97 constitutive androstane receptor (CAR) and pregnane X-receptor (PXR) are two nuclear receptors involved in chemical detoxication, and associated with metabolic diseases although possibly in opposing directions.
0.96 CAR activation alleviates symptoms of obesity and fatty liver disease and murine PXR activation increases obesity, although there are conflicting reports on PXR's effects on obesity and insulin resistance.
0.83 CAR, or potentially Cyp2b10, a gene controlled by the nuclear receptors CAR and PXR (Suppl.
26924429 0.97 PXR and CAR also can regulate overlapped and distinctive sets of genes involved in xenobiotic metabolism.
0.96 PXR, another xenobiotic receptor, constitutive androstane receptor (CAR; NR1I3 for standard nomenclature) also has a broad role in xenobiotic metabolism.
0.96 PXR, CAR shows relatively high basal activity to activate target genes without ligand.
25542016 0.97 CAR and/or PXR, CCRP could regulate them either independently or by co-regulating nuclear receptors.
0.51 CAR, CCRP also interacted with GR, mineralocorticoid receptor, progesterone receptor (PR), estrogen receptor, androgen receptor and pregnane X receptor (PXR).
25714878 0.97 NR1I2 is another nuclear receptor that closely resembles NR1I3 in function and homology; it has a controversial role in cancer pathogenesis and multi-drug resistance.
0.96 NR1I3 and NR1I2 (pregnane-X receptor, PXR) by specific ligands, combined with chemotherapeutics might attenuate, or even overcome, multi-drug resistance in cancer cells.
28793934 0.97 Pxr -/- mice and the higher levels of the sulphate-conjugated BA 7-SCA in the Pxr -/- mice receiving pravastatin may suggest that pravastatin also activates CAR in vivo.
0.92 CAR and PXR may explain the contrasting diabetogenic character of both drugs.
30361333 0.97 CAR activators also activate the pregnane X receptor (PXR) resulting in induction of the same proteins.
0.67 CAR, for example on a Pxr null background.
20979450 0.97 PXR or CAR, thus indicating that the induction of Cyp3a11 by BC may act through activation of PXR or CAR.
21672546 0.97 Pregnane X Receptor (PXR), Constitutive Androstane Receptor (CAR), and others.
31374856 0.97 constitutive androstane receptor (CAR), and PXR, which were historically described as xenobiotic sensors, can also interact with the hormone-responsive transcription factors to regulate the liver metabolic processes.
30620001 0.96 CAR and PXR in the induction of a range of drug metabolism genes22 and the direct activation of PXR by elevated BA levels.38 In accord with this, we previously found that combined CAR/PXR deletion in the DKO background (Fxr;Shp;Car;Pxr quadruple knockout) completely abolished CYP gene induction.10 This impairs bilirubin-conjugation processes and results in a dramatic accumulation of indirect bilirubin.
18692084 0.95 PXR, induction of P4502B10, 3A11, and 2C9 by xenobiotics may also be mediated by the constitutive androstane receptor (CAR).
0.95 PXR, SXR and CAR, and that the induction of Cyp2b10 mRNA may be mediated through its interactions with CAR.
0.94 pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR).
29184608 0.93 PXR and CAR as mechanistic links between microbes and host.
21801835 0.86 PXR is most closely related to CAR (NR1I3, Constitutive Androstane Receptor); the two receptors share ~70% amino acid identity in their LBDs, and they also have an overlapping target gene pattern.
30102401 0.65 CAR/PXR rodent models are being deployed to facilitate hepatocarcinogenesis studies and to inform toxicology investigations in industry.
0.51 CAR exhibited significant binding to various receptors' promoter regions, including hepatocyte nuclear factor 4 alpha (Hnf4a), retinoic acid recetor beta ( Rarb), retinoid X receptor beta ( Rxrb), PXR (Nr1i2), peroxisome proliferator activated receptor delta (Ppard), estrogen receptor alpha (Esr1), COUP transcription factor 2 (Nr2f2), small heterodimer partner (Nr0b2; Shp1), as well as aryl hydrocarbon receptor (Ahr;AHR), and CAR (Nr1i3) itself.



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