Ask about this productRelated genes to: NR1I2 antibody
- Gene:
- NR1I2 NIH gene
- Name:
- nuclear receptor subfamily 1 group I member 2
- Previous symbol:
- -
- Synonyms:
- ONR1, PXR, BXR, SXR, PAR2
- Chromosome:
- 3q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-23
- Date modifiied:
- 2016-10-05
Related products to: NR1I2 antibody
Related articles to: NR1I2 antibody
- The pregnane X receptor (PXR) gene encodes a ligand-activated protein involved with the metabolism and excretion of drugs, toxins, and other xenobiotics. The PXR protein is also an orphan nuclear receptor with a broad spectrum of potential ligands, including common prescription drugs, that can act as agonists or antagonists. Once activated, PXR upregulates several target genes involved in xenobiotic metabolism and can influence lipid and glucose metabolism, as well as the metabolism of commonly used drugs. In this review we searched the primary literature for articles reporting on drugs that regulate PXR and discuss potential clinical implications. Using the databases CINAHL, Embase, Medline, Scopus and Web of Science, we searched for terms related to PXR, following PRISMA guidelines. We screened 12 236 studies, 101 of which met the inclusion criteria, and included a further 46 research and review articles. We identified 42 studies reporting on prescription medications and 40 on non-prescription medications that regulate PXR as agonists or antagonists, and 47 studies reporting both beneficial and detrimental PXR-mediated effects of drugs on specific diseases, including different cancers, metabolic diseases, and inflammatory conditions, among others. We conclude that PXR is regulated by a broad range of drugs. Downstream effects of this regulation affect different diseases, leading to clinically relevant outcomes, such as altered efficacy of drugs or changes to the pathophysiology of a disease. Understanding and managing the agonist or antagonist role of drugs on PXR holds great potential to improve the health outcomes of different diseases. However, more information is needed about the potency of known PXR regulators. - Source: PubMed
Czarniak PetraMoorin RachaelHughes JeffGruber KarlYouens David - Current therapeutic strategies for senile osteoporosis inadequately address its low-turnover pathology driven by mitochondrial dysfunction and cellular senescence. This study identifies menaquinone-7 (MK-7), a vitamin K isoform, as a novel therapeutic agent targeting mitochondrial homeostasis in senile osteoporosis. Through RNA sequencing analysis and intramedullary adeno-associated virus (AAV)-based gene manipulation in aged mice, cellular communication network factor 2 (Ccn2) was identified as a critical mediator of MK-7's bone-protective effects. Biochemical and proteomic assays revealed that MK-7 binds to the nuclear receptor pregnane X receptor (PXR), activating the extracellular signal-regulated kinases 1/2 (ERK1/2)/cyclic AMP-responsive element-binding protein (CREB) signaling cascade to upregulate Ccn2 in senescent bone marrow mesenchymal stem cells (BMSCs). This pathway enhanced PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy, reducing mitochondrial DNA damage, reactive oxygen species (mtROS), and senescence-associated secretory phenotype (SASP), while restoring metabolic function. MK-7 redirected BMSC differentiation from adipogenic to osteogenic lineages, effectively mitigating age-related bone loss . Mechanistically, MK-7 stabilized PXR via direct interaction at the F285 residue, as confirmed by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular docking. PXR activation further promoted ERK1/2/CREB-dependent Ccn2 expression, which orchestrated mitochondrial quality control and cellular energy metabolism. Our findings establish MK-7 as a dual-function agent that concurrently alleviates senescence and metabolic imbalance in bone tissue, offering a safe and targeted strategy for senile osteoporosis. This study provides critical insights into the pharmacological modulation of mitochondrial pathways and highlights MK-7's translational potential in geriatric bone health. - Source: PubMed
Publication date: 2025/08/09
Xu YuZhang WencanXu WenpengLi ShangzhiZhang DingxinLin XiangyuLiu JinchengFu QingyangHu PeijieSi Haipeng - Zearalenone (ZEA) is a mycotoxin frequently detected in food. Cyanidin-3-glucoside (C3G), an anthocyanin abundant in food, exhibits regulatory effects on hepatic metabolism; however, its role in ZEA-induced hepatic lipotoxicity remains unclear. In this study, C57BL/6 J mice were exposed to low-dose ZEA (0.5 mg/kg·bw) combined with a combined with a high-fat diet (HFD) for 96 days, and HepG2 and HepaRG cells were treated with ZEA and oleic acid to investigate chronic ZEA-induced metabolic disturbances. C3G was administered to evaluate its protective effects. ZEA disrupted hepatic energy metabolism, promoted lipid accumulation, and induced more severe lipotoxicity. Mechanistically, ZEA activated the pregnane X receptor (PXR), upregulating fatty acid transporters CD36 and FABP4, thereby enhancing fatty acid uptake and lipid synthesis. C3G inhibits ZEA-induced PXR activation, thereby suppressing PXR signaling and alleviating ZEA-induced hepatic lipotoxicity under HFD conditions. Collectively, C3G mitigates ZEA-induced hepatic lipotoxicity by inhibiting PXR activation, highlighting anthocyanins as potential interventions against mycotoxin-associated metabolic injury. - Source: PubMed
Publication date: 2026/06/10
Huangfu BingxinWang TengCai DongbaoXu JiaHuang KunlunLiang ZhihongBai WeibinHe Xiaoyun - Pregnancy induces or represses hepatic drug metabolism. Whether pregnancy affects hepatic drug transport is unexplored. We previously showed that a cocktail of pregnancy-related hormones (PRHC) induces mRNA expression and activity of sodium/taurocholate cotransporting polypeptide (NTCP), organic anion transporter 2 (OAT2), and organic cation transporter 1 (OCT1, mRNA only) in differentiated HepaRG cells. Here, using HepaRG cells, we identified cortisol as the hormone primarily responsible for this induction and explored the underlying mechanisms. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated knockdown studies in HepaRG cells showed that the glucocorticoid receptor (GR) is the primary mediator of this response. GR knockdown markedly attenuated cortisol-induced NTCP, OAT2, and OCT1 mRNA expression and activity. Cortisol also induced the mRNA expression of regulatory factors, including pregnane X receptor (PXR), constitutive androstane receptor (CAR), and hepatocyte nuclear factor (HNF) 4 alpha (HNF4α). HNF4α knockdown selectively attenuated OAT2 and OCT1 induction, whereas HNF1α knockdown enhanced NTCP induction, attenuated OCT1 induction, and reduced basal organic anion transporting polypeptide 1B1 (OATP1B1) expression. In contrast, knockdown of CAR or PXR did not significantly alter cortisol-mediated transporter regulation. These data identify cortisol as the principal PRH driving regulation of the hepatic OAT2, NTCP, and OCT1 in HepaRG cells and indicate that this response is mediated primarily by GR, with selective downstream contributions from HNF4α and HNF1α. These findings provide mechanistic insights into pregnancy-associated changes in hepatic transporter-mediated drug disposition, including when antenatal corticosteroids are administered to pregnant women to prevent respiratory distress syndrome in their prematurely born infants. - Source: PubMed
Publication date: 2026/06/19
Sharma SejalTsang Yik PuiUnadkat Jashvant D - High-fat diet (HFD)-associated anxiety- and depression-like behaviors are closely linked to disturbances in the gut-brain axis; however, the peripheral signaling mechanisms and key metabolites involved remain to be elucidated. Deoxycholic acid (DCA), a bile acid elevated by a HFD, has been reported to be associated with abnormal cognitive behaviors in mice. This study aimed to investigate whether HFD-induced anxiety- and depression-like behaviors are regulated by intestinal DCA and its underlying mechanisms. - Source: PubMed
Publication date: 2026/06/11
Wu YulunLiu LehengYou DandanMao TianchengZheng XinboDai XinXu XianjunWu XiaowanZhou Hui