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PXR is upregulated in the diabetic kidney with aberrant epigenetic modifications and may modulate the course of diabetic kidney disease through the activation of metabolic genes.
Study suggests increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis.
This meta-analysis indicates that the rs3814057 and rs3814058 polymorphisms of PXR gene play crucial roles in the pathogenesis of cancer and may be novel biomarkers for cancer-forewarning in overall population or in some particular subgroups. (Review, Meta-analysis)
Crosstalk between BCR-ABL1 and PAR1 suggests a novel target in chronic myeloid leukemia.
Data suggest that PXR in macrophages mediates rifampicin/antituberculosis drug non-responsiveness of Mycobacterium tuberculosis by modulating expression of drug-efflux transporters in macrophages; this study utilized rifampicin-susceptible Mycobacterium tuberculosis H37Rv and rifampicin-resistant Mycobacterium tuberculosis Zopf.
EGF suppresses specifically CAR signaling mainly through transcriptional regulation and drives the xenobiotic response toward a pregnane X receptor (PXR)-mediated mechanism.
The bosutinib C0 in patients with the NR1I2 7635G/G or 8055T/T genotype was significantly lower than those in patients with the 7635A allele or 8055C allele.
An overview of NR1I2 and NR1I3 pharmacogenetic studies in various therapeutic fields.
We demonstrated that small interfering RNA (siRNA)-mediated knockdown of PRR, Nox2 and Nox4 significantly reduced the HG-induced stimulation of VEGF. On the other hand, Nox4 overexpression significantly potentiated PRR-induced stimulation of VEGF under hyperglycemia in ARPE-19 cells.
The pregnane X receptor (PXR) and the nuclear receptor corepressor 2 (NCoR2) modulate cell growth in head and neck squamous cell carcinoma.
High endogenous pregnane X receptor (PXR) level is associated with poor sorafenib therapy outcome.
A total of six studies with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene polymorphism had no obvious influence on the risk of inflammatory bowel disease in Caucasians.
genotypes and haplotypes of PXR rs3814057, rs3814058 and rs6785049 have impact on the major adverse cardiovascular events in clopidogrel treated patients after percutaneous coronary intervention
replication confirmed at genome-wide significance the association of loci at FOXE1 with hypothyroidism, and PDE8B, CAPZB and PDE10A with serum TSH. A total of 12 SNPs seemed to explain nearly 7% of the serum TSH variation
NR1I2 has a role in promoting stem cell-mediated colon cancer relapse
Dual ligands of CAR/PXR show distinct gene regulation patterns by regulating cross-talk between CAR and PXR.
High PXR expression is associated with multidrug resistance in breast cancer.
PXR, CYP3A4, and VIL1 expression was decreased only in the actively inflamed small intestinal tissue in children with Crohn's disease.
NR1I2 g.7635A>G had a significant interaction with time, but the dose-adjusted tacrolimus concentration did not significantly differ over 5 years post-transplantation, except for the GG genotype of NR1I2 g.7635A>G.
Together, our results suggest that protection of the endothelial barrier by APC/TR47-mediated signaling pathways might be a valuable therapeutic approach to prevent metastasis
Data suggest that expression of pregnane X receptor (PXR) is correlated with expression of CYP3A29 in hepatocytes. (CYP3A29 = cytochrome P450 family 3 subfamily A polypeptide 29)
The regulatory effect of IFN-gamma on CYP3A29 expression is mediated via PXR.
Pregnane X receptor is required for interferon-alpha-mediated CYP3A29 expression, and its expression before CYP3A29.
In conclusion, PXR and FXR both responded to ligands that activated their human orthologs, and some of the alternatively spliced variants significantly altered PXR and FXR transactivation at in vivo expression levels.
the PXR gene revealed multiple splice variants in the ligand-binding domain
Absence of PXR was associated with anxiety-like behavior and recognition memory impairment in adult mice. The latter was simultaneous to an EEG signature of lower theta frequency during sleep and abnormal delta waves. Neurophysiological changes did not correspond to significant structural changes in the adult brain, expect for a localized and minor increase in the fronto-parietal neurovascular density and reduced ZO1.
Pregnane X receptor (PXR, NR1I2) is a crucial regulator of nutrient metabolism and metabolic detoxification. PXR senses xenobiotics and triggers the detoxification response to prevent diseases such as diabetes, obesity, intestinal inflammatory diseases and liver fibrosis. Review.
PXR deficiency suppresses chronic Ethanol-induced lipogenic gene induction.
Results demonstrate that PXR acts as a rheostat in fine tuning the balance of innate inflammatory pathways through TLR4 to ensure protective immunity.
Data suggest that regulation of SXR expression is involved in nephrosis induced by environmental poisons; here, nephrosis caused by atrazine herbicide poisoning can be mitigated by supplementation with antioxidant lycopene; in the kidney, mechanisms involved include modulation of SXR expression and of SXR transport to the nucleus.
FXR signaling is a bile acid nuclear receptor that regulates lipids and glucose homeostasis and lack of it causes hepatomegaly and liver dysfunction.
Both the acetylation and SUMOylation status of the PXR protein is affected by its ability to associate with the lysine de-acetylating enzyme HDAC3 in a complex with SMRT.
The present study has revealed known and novel, as well as common and unique targets of PXR and CAR in mouse liver following pharmacological activation using their prototypical ligands.
FGF21-PXR signaling pathway may be involved in decreased hepatic CYP3A4 metabolic activity in Nonalcoholic fatty liver disease.
Pregnenolone 16alpha-carbonitrile has immunosuppressive activity independent of PXR activation to protect mice from immune-mediated liver injury induced by Con A.
carcinogens might trigger PXR in epidermal cells, particularly in Langerhans cells, leading to DNA damage
PXR activation stimulates EGF-mediated hepatocyte proliferation in mice, at least in part, through inhibiting FOXO3 from accelerating cell-cycle progression.
The role of intestinal PXR in linking xenobiotic exposure and hyperlipidemia.
modulation of vemurafenib bioavailability through pregnane X receptor-mediated regulation of drug transporters has the potential to markedly influence systemic exposure and thereby therapeutic outcomes.
results indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging.
Suggest a novel role for PXR signaling in the maintenance of intestinal homeostasis and may help to elucidate additional mechanisms through which PXR signaling is protective in inflammatory bowel disease.
a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.
Role of pregnane X receptor in obesity and glucose homeostasis
Xenobiotic-induced hepatocyte proliferation mediated by CAR or PPARalpha is enhanced by PXR co-activation despite the fact that PXR activation alone does not cause the cell proliferation in mouse livers.
Selected zebrafish CYP1, CYP2 and CYP3 genes appear to be under the regulation of both pregnane X receptor and aryl hydrocarbon receptor 2.
CYP3A65 and PXR may be involved in the metabolization and detoxification of microcystins in zebrafish, which may be regulated by dre-miR-27b.
similar pattern of mRNA expression of PXR, cytochrome P4503A and multiple drug resistance 1 genes found in fish treated with different PXR inducers suggests that the intrinsic association between these three genes is conserved in zebrafish
This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized.
nuclear receptor subfamily 1 group I member 2
, orphan nuclear receptor PAR1
, orphan nuclear receptor PXR
, pregnane X nuclear receptor variant 2
, pregnane X receptor
, steroid and xenobiotic receptor
, Pregnane X receptor
, nuclear receptor subfamily 1, group 1, member 2
, pregnane X receptor (nuclear receptor sub family 1, group I, member 2)
, nuclear receptor subfamily 1 group I member 2 S homeolog
, nuclear receptor subfamily 1, group I, member 2
, orphan nuclear receptor BXR-beta