Nr1i2

Summary

Gene Symbol: Nr1i2
Description: nuclear receptor subfamily 1, group I, member 2
Alias: PXR, PXR.1, PXR.2, PXR1, SXR, mPXR, nuclear receptor subfamily 1 group I member 2, Pregnane X receptor, orphan nuclear receptor PXR
Species: mouse
Products:     Nr1i2

Top Publications

  1. Lehmann J, McKee D, Watson M, Willson T, Moore J, Kliewer S. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998;102:1016-23 pubmed
    ..We report the identification of a human (h) orphan nuclear receptor, termed the pregnane X receptor (PXR), that binds to a response element in the CYP3A4 promoter and is activated by a range of drugs known ..
  2. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H, Toma D, et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem. 2006;281:15013-20 pubmed
    The pregnane X receptor (PXR) was isolated as a xenosensor regulating xenobiotic responses. In this study, we show that PXR plays an endobiotic role by impacting lipid homeostasis...
  3. Johnson D, Li C, Chen L, Ghosh J, Chen J. Regulation and binding of pregnane X receptor by nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT). Mol Pharmacol. 2006;69:99-108 pubmed
    The pregnane X receptor (PXR) is an orphan nuclear receptor predominantly expressed in liver and intestine. PXR coordinates hepatic responses to prevent liver injury induced by environmental toxins...
  4. Xie W, Yeuh M, Radominska Pandya A, Saini S, Negishi Y, Bottroff B, et al. Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci U S A. 2003;100:4150-5 pubmed
    ..The orphan nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) were originally identified as sensors able to respond to ..
  5. Cheng J, Krausz K, Tanaka N, Gonzalez F. Chronic exposure to rifaximin causes hepatic steatosis in pregnane X receptor-humanized mice. Toxicol Sci. 2012;129:456-68 pubmed publisher
    ..a nonsystemic antibiotic that exhibits low gastrointestinal absorption, is a potent agonist of human pregnane X receptor (PXR), which contributes to its therapeutic efficacy in inflammatory bowel disease...
  6. Zhang J, Huang W, Qatanani M, Evans R, Moore D. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem. 2004;279:49517-22 pubmed
    ..line (2XENKO) lacking the xenobiotic receptors CAR (constitutive androstane receptor) (NR1I3) and PXR (pregnane X receptor) (NR1I2) was generated to study their functions in response to potentially toxic xenobiotic and endobiotic ..
  7. Azuma K, Casey S, Ito M, Urano T, Horie K, Ouchi Y, et al. Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption. J Endocrinol. 2010;207:257-63 pubmed publisher
    The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors...
  8. Zhou C, Tabb M, Nelson E, Grün F, Verma S, Sadatrafiei A, et al. Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. J Clin Invest. 2006;116:2280-2289 pubmed
    ..are upregulated and small bowel inflammation is significantly increased in mice lacking the SXR ortholog pregnane X receptor (PXR), thereby demonstrating a direct link between SXR and drug-mediated antagonism of NF-kappaB...
  9. Staudinger J, Goodwin B, Jones S, Hawkins Brown D, MacKenzie K, LaTour A, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001;98:3369-74 pubmed
    The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such as pregnenolone 16alpha-carbonitrile (PCN), which induce cytochrome P450 3A (CYP3A) expression and protect the body from harmful chemicals...

More Information

Publications83

  1. Jones S, Moore L, Shenk J, Wisely G, Hamilton G, McKee D, et al. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol. 2000;14:27-39 pubmed publisher
    ..Recently, the mouse and human pregnane X receptor (PXR) were shown to be activated by compounds that induce CYP3A expression...
  2. Staudinger J, Liu Y, Madan A, Habeebu S, Klaassen C. Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Drug Metab Dispos. 2001;29:1467-72 pubmed
    Identification and characterization of the pregnane X receptor (PXR) as a key regulator of cytochrome P450 3A (CYP3A) gene expression has led to an increased understanding of the molecular basis of many drug-drug interactions...
  3. Saini S, Mu Y, Gong H, Toma D, Uppal H, Ren S, et al. Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice. Hepatology. 2005;41:497-505 pubmed
    The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are implicated in xenobiotic and endobiotic detoxification, including the clearance of toxic bilirubin...
  4. Dai G, He L, Bu P, Wan Y. Pregnane X receptor is essential for normal progression of liver regeneration. Hepatology. 2008;47:1277-87 pubmed publisher
    b>Pregnane X receptor (PXR) mediates xenobiotic and endobiotic metabolism as well as hepatocyte proliferation. To determine the role of PXR in liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and PXR-null mice...
  5. Shah Y, Ma X, Morimura K, Kim I, Gonzalez F. Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kappaB target gene expression. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1114-22 pubmed
    b>Pregnane X receptor (PXR) expression was shown to be protective in inflammatory bowel disease (IBD). However, the mechanism by which PXR provides protection remains unclear...
  6. Kliewer S, Willson T. Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor. J Lipid Res. 2002;43:359-64 pubmed
    The nuclear pregnane X receptor (PXR; NR1I2) is an integral component of the body's defense mechanism against chemical insult (chemoprotection)...
  7. Gong H, Singh S, Singh S, Mu Y, Lee J, Saini S, et al. Orphan nuclear receptor pregnane X receptor sensitizes oxidative stress responses in transgenic mice and cancerous cells. Mol Endocrinol. 2006;20:279-90 pubmed
    ..Efficient handling of oxidative stress is critical for the survival of organisms. The orphan nuclear receptor pregnane X receptor (PXR) is important in xenobiotic detoxification through its regulation of phase I and phase II drug-..
  8. Kliewer S, Moore J, Wade L, Staudinger J, Watson M, Jones S, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998;92:73-82 pubmed
    ..We describe a novel orphan nuclear receptor, termed the pregnane X receptor (PXR), that is activated by naturally occurring steroids such as pregnenolone and progesterone, and ..
  9. Kodama S, Koike C, Negishi M, Yamamoto Y. Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol. 2004;24:7931-40 pubmed
    The nuclear receptors CAR and PXR activate hepatic genes in response to therapeutic drugs and xenobiotics, leading to the induction of drug-metabolizing enzymes, such as cytochrome P450...
  10. Wang H, Venkatesh M, Li H, Goetz R, Mukherjee S, Biswas A, et al. Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice. J Clin Invest. 2011;121:3220-32 pubmed publisher
    The nuclear receptor pregnane X receptor (PXR) is activated by a range of xenochemicals, including chemotherapeutic drugs, and has been suggested to play a role in the development of tumor cell resistance to anticancer drugs...
  11. Nakamura K, Moore R, Negishi M, Sueyoshi T. Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver. J Biol Chem. 2007;282:9768-76 pubmed
    Upon drug activation, the nuclear pregnane X receptor (PXR) regulates not only hepatic drug but also energy metabolism. Using Pxr(-/-) mice, we have now investigated the PXR-mediated repression of lipid metabolism in the fasting livers...
  12. Xie W, Barwick J, Downes M, Blumberg B, Simon C, Nelson M, et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature. 2000;406:435-9 pubmed
    ..as the nuclear receptor pregnenolone X receptor (PXR) and its human homologue, steroid and xenobiotic receptor (SXR)...
  13. Hagedorn K, Cooke C, Falck J, Mitchell B, Davidge S. Regulation of vascular tone during pregnancy: a novel role for the pregnane X receptor. Hypertension. 2007;49:328-33 pubmed
    ..Progesterone metabolites are potent endogenous ligands for the pregnane X receptor (PXR), a nuclear receptor that induces the expression of hepatic cytochrome P450 enzymes...
  14. Blumberg B, Sabbagh W, Juguilon H, Bolado J, van Meter C, Ong E, et al. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 1998;12:3195-205 pubmed
    ..In support of this model, we have isolated a novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), which activates transcription in response to a diversity of natural and synthetic compounds...
  15. Wallace K, Cowie D, Konstantinou D, Hill S, Tjelle T, Axon A, et al. The PXR is a drug target for chronic inflammatory liver disease. J Steroid Biochem Mol Biol. 2010;120:137-48 pubmed publisher
    b>PXR activators are used to treat pruritus in chronic inflammatory liver diseases such as primary biliary cirrhosis (PBC)...
  16. Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, He J, et al. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology. 2008;134:556-67 pubmed publisher
    ..b>Pregnane X receptor (PXR), a previously known "xenobiotic receptor," could mediate a Srebp-independent lipogenic ..
  17. Zhou C, King N, Chen K, Breslow J. Activation of PXR induces hypercholesterolemia in wild-type and accelerates atherosclerosis in apoE deficient mice. J Lipid Res. 2009;50:2004-13 pubmed publisher
    The nuclear hormone receptor pregnane X receptor (PXR; also called SXR) functions as a xenobiotic sensor to coordinately regulate xenobiotic metabolism via transcriptional regulation of xenobiotic-detoxifying enzymes and transporters...
  18. He J, Gao J, Xu M, Ren S, Stefanovic Racic M, O Doherty R, et al. PXR ablation alleviates diet-induced and genetic obesity and insulin resistance in mice. Diabetes. 2013;62:1876-87 pubmed publisher
    The pregnane X receptor (PXR), along with its sister receptor constitutive androstane receptor (CAR), was initially characterized as a xenobiotic receptor that regulates drug metabolism...
  19. Gartner H, Graul M, Oesterreicher T, Finegold M, Henning S. Development of the fetal intestine in mice lacking the glucocorticoid receptor (GR). J Cell Physiol. 2003;194:80-7 pubmed
    ..Neither the minerolocorticoid receptor (MR) nor the pregnane X receptor (PXR) showed compensatory up-regulation in GR-/- mice...
  20. Scheer N, Balimane P, Hayward M, Buechel S, Kauselmann G, Wolf C. Generation and characterization of a novel multidrug resistance protein 2 humanized mouse line. Drug Metab Dispos. 2012;40:2212-8 pubmed publisher
    ..The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2. ..
  21. Wang X, Fang X, Zhou J, Chen Z, Zhao B, Xiao L, et al. Shear stress activation of nuclear receptor PXR in endothelial detoxification. Proc Natl Acad Sci U S A. 2013;110:13174-9 pubmed publisher
    ..b>Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics...
  22. Cui J, Gunewardena S, Rockwell C, Klaassen C. ChIPing the cistrome of PXR in mouse liver. Nucleic Acids Res. 2010;38:7943-63 pubmed publisher
    The pregnane X receptor (PXR) is a key regulator of xenobiotic metabolism and disposition in liver. However, little is known about the PXR DNA-binding signatures in vivo, or how PXR regulates novel direct targets on a genome-wide scale...
  23. Xu D, Wei W, Sun M, Wu C, Wang J, Wei L, et al. Kupffer cells and reactive oxygen species partially mediate lipopolysaccharide-induced downregulation of nuclear receptor pregnane x receptor and its target gene CYP3a in mouse liver. Free Radic Biol Med. 2004;37:10-22 pubmed
    b>Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that regulates target gene transcription in a ligand-dependent manner...
  24. Zhai Y, Pai H, Zhou J, Amico J, Vollmer R, Xie W. Activation of pregnane X receptor disrupts glucocorticoid and mineralocorticoid homeostasis. Mol Endocrinol. 2007;21:138-47 pubmed
    The pregnane X receptor (PXR) was isolated as a xenobiotic receptor that regulates responses to various xenobiotic agents. In this study, we show that PXR plays an important endobiotic role in adrenal steroid homeostasis...
  25. Ding X, Lichti K, Kim I, Gonzalez F, Staudinger J. Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor alpha, and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha. J Biol Chem. 2006;281:26540-51 pubmed
  26. Saradhi M, Sengupta A, Mukhopadhyay G, Tyagi R. Pregnane and Xenobiotic Receptor (PXR/SXR) resides predominantly in the nuclear compartment of the interphase cell and associates with the condensed chromosomes during mitosis. Biochim Biophys Acta. 2005;1746:85-94 pubmed
    Pregnane and Xenobiotic Receptor (PXR) is a transcription factor that is activated by a diverse range of xenobiotics and endogenous metabolites including steroids, bile acids and about 50% of the prescription drugs...
  27. Teng S, Piquette Miller M. The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J Pharmacol Exp Ther. 2005;312:841-8 pubmed
    ..However, mechanism(s) of this down-regulation have not been fully elucidated. As the pregnane X receptor (PXR) is involved in inducing many of these hepatic proteins, it is possible that PXR is also involved in ..
  28. Xie Y, Ke S, Ouyang N, He J, Xie W, Bedford M, et al. Epigenetic regulation of transcriptional activity of pregnane X receptor by protein arginine methyltransferase 1. J Biol Chem. 2009;284:9199-205 pubmed publisher
    b>Pregnane X receptor (PXR) is a ligand-dependent transcription factor, regulating gene expression of enzymes and transporters involved in xenobiotic/drug metabolism...
  29. Konno Y, Moore R, Kamiya N, Negishi M. Nuclear xenobiotic receptor PXR-null mouse exhibits hypophosphatemia and represses the Na/Pi-cotransporter SLC34A2. Pharmacogenet Genomics. 2010;20:9-17 pubmed publisher
    We previously found that the lack of nuclear xenobiotic receptor, PXR, decreases femoral bone mineral density (BMD) in Pxr-/- mice...
  30. Wang K, Damjanov I, Wan Y. The protective role of pregnane X receptor in lipopolysaccharide/D-galactosamine-induced acute liver injury. Lab Invest. 2010;90:257-65 pubmed publisher
    The pregnane X receptor (PXR) is a nuclear receptor transcription factor regulating drug-metabolizing enzymes and transporters that facilitate xenobiotic and endobiotic detoxification...
  31. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow Bäckman M, et al. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci U S A. 1998;95:12208-13 pubmed
    ..16alpha-carbonitrile, which is a potent inducer of murine CYP3A genes and an activator of the mouse receptor PXR.1...
  32. Sonoda J, Chong L, Downes M, Barish G, Coulter S, Liddle C, et al. Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites. Proc Natl Acad Sci U S A. 2005;102:2198-203 pubmed
    ..We report here that loss of the nuclear xenobiotic receptor PXR (pregnane X receptor), a regulator of enterohepatic drug metabolism and clearance, results in an unexpected acute lethality ..
  33. Cui Y, Aleksunes L, Tanaka Y, Goedken M, Klaassen C. Compensatory induction of liver efflux transporters in response to ANIT-induced liver injury is impaired in FXR-null mice. Toxicol Sci. 2009;110:47-60 pubmed publisher
    ..Farnesoid X receptor (FXR) and pregnane X receptor (PXR) are two major bile acid sensors in liver...
  34. Saini S, Sonoda J, Xu L, Toma D, Uppal H, Mu Y, et al. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol. 2004;65:292-300 pubmed
    ..Therefore, we establish an essential and unique role of CAR in controlling the mammalian sulfation system and its implication in the detoxification of bile acids. ..
  35. Squires E, Sueyoshi T, Negishi M. Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem. 2004;279:49307-14 pubmed
    The pregnane X receptor (PXR) plays an important role in the response to xenobiotics and endogenous toxins...
  36. Guo G, Moffit J, Nicol C, Ward J, Aleksunes L, Slitt A, et al. Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci. 2004;82:374-80 pubmed
    The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily...
  37. Roth A, Looser R, Kaufmann M, Blättler S, Rencurel F, Huang W, et al. Regulatory cross-talk between drug metabolism and lipid homeostasis: constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol Pharmacol. 2008;73:1282-9 pubmed publisher
    Activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) by xenobiotic inducers of cytochromes P450 is part of a pleiotropic response that includes liver hypertrophy, tumor promotion, effects on lipid ..
  38. Zhou C, Assem M, Tay J, Watkins P, Blumberg B, Schuetz E, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006;116:1703-12 pubmed
    ..Moreover, 1,25(OH)2D3-induced CYP24 expression was enhanced in mice lacking the SXR ortholog pregnane X receptor, and treatment of humans with the SXR agonist rifampicin had no effect on intestinal CYP24 expression, ..
  39. Masson D, Lagrost L, Athias A, Gambert P, Brimer Cline C, Lan L, et al. Expression of the pregnane X receptor in mice antagonizes the cholic acid-mediated changes in plasma lipoprotein profile. Arterioscler Thromb Vasc Biol. 2005;25:2164-9 pubmed
    ..The aim of the present study was to determine the relative contribution of the pregnane X receptor (PXR), another bile acid-activated nuclear receptor to changes in plasma lipoprotein profile.
  40. Buler M, Aatsinki S, Skoumal R, Hakkola J. Energy sensing factors PGC-1? and SIRT1 modulate PXR expression and function. Biochem Pharmacol. 2011;82:2008-15 pubmed publisher
    The pregnane X receptor (PXR), a xenobiotic-sensing nuclear receptor plays a major role in regulation of drug metabolism but also modulates hepatic energy metabolism...
  41. Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet A, et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014;41:296-310 pubmed publisher
    ..showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR)...
  42. Shizu R, Benoki S, Numakura Y, Kodama S, Miyata M, Yamazoe Y, et al. Xenobiotic-induced hepatocyte proliferation associated with constitutive active/androstane receptor (CAR) or peroxisome proliferator-activated receptor ? (PPAR?) is enhanced by pregnane X receptor (PXR) activation in mice. PLoS ONE. 2013;8:e61802 pubmed publisher
    Xenobiotic-responsive nuclear receptors pregnane X receptor (PXR), constitutive active/androstane receptor (CAR) and peroxisome proliferator-activated receptor ? (PPAR?) play pivotal roles in the metabolic functions of the liver such as ..
  43. Bauer B, Yang X, Hartz A, Olson E, Zhao R, Kalvass J, et al. In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Mol Pharmacol. 2006;70:1212-9 pubmed
    ..studies in rat showed that brain capillary P-glycoprotein was transcriptionally up-regulated by the pregnane X receptor (PXR), a xenobiotic-activated nuclear receptor...
  44. Stedman C, Liddle C, Coulter S, Sonoda J, Alvarez J, Evans R, et al. Benefit of farnesoid X receptor inhibition in obstructive cholestasis. Proc Natl Acad Sci U S A. 2006;103:11323-8 pubmed
    The nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor have been implicated in regulating bile acid, lipid, carbohydrate, and xenobiotic metabolism...
  45. Breuker C, Moreau A, Lakhal L, Tamasi V, Parmentier Y, Meyer U, et al. Hepatic expression of thyroid hormone-responsive spot 14 protein is regulated by constitutive androstane receptor (NR1I3). Endocrinology. 2010;151:1653-61 pubmed publisher
    ..that CAR directly transactivates THRSP promoter through the direct repeat with 4-bp spacer thyroid hormone and PXR response element...
  46. Poulton E, Levy L, Lampe J, Shen D, Tracy J, Shuhart M, et al. Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo. Toxicol Appl Pharmacol. 2013;266:122-31 pubmed publisher
    ..SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR)...
  47. Shizu R, Abe T, Benoki S, Takahashi M, Kodama S, Miayata M, et al. PXR stimulates growth factor-mediated hepatocyte proliferation by cross-talk with the FOXO transcription factor. Biochem J. 2016;473:257-66 pubmed publisher
    ..The nuclear receptor, pregnane X receptor (PXR), is a key transcription factor for the xenobiotic-induced expression of genes associated with various ..
  48. Mongan M, Dunn R, Vonderfecht S, Everds N, Chen G, Su C, et al. A novel statistical algorithm for gene expression analysis helps differentiate pregnane X receptor-dependent and independent mechanisms of toxicity. PLoS ONE. 2010;5:e15595 pubmed publisher
    ..These two methods were applied to investigate hepatic transcriptional responses of wild-type (PXR(+/+)) and pregnane X receptor-knockout (PXR(-/-)) mice after 96 h exposure to CMP013, an inhibitor of ?-secretase (?-site of amyloid ..
  49. Aleksunes L, Klaassen C. Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPAR?-, and Nrf2-null mice. Drug Metab Dispos. 2012;40:1366-79 pubmed publisher
    The transcription factors aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor ? (PPAR?), and nuclear factor erythroid 2-related factor 2 (Nrf2) ..
  50. Dong B, Qatanani M, Moore D. Constitutive androstane receptor mediates the induction of drug metabolism in mouse models of type 1 diabetes. Hepatology. 2009;50:622-9 pubmed publisher
    ..of the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane and xenobiotic receptor (PXR) in this process...
  51. Handschin C, Podvinec M, Meyer U. CXR, a chicken xenobiotic-sensing orphan nuclear receptor, is related to both mammalian pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Proc Natl Acad Sci U S A. 2000;97:10769-74 pubmed
    ..xenobiotic receptor (CXR), that is closely related to two mammalian xenobiotic-activated receptors, the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR)...
  52. Uppal H, Toma D, Saini S, Ren S, Jones T, Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. Hepatology. 2005;41:168-76 pubmed
    ..The orphan nuclear receptors PXR and CAR have been proposed to play an important role in the detoxification of xeno- and endo-biotics by regulating ..
  53. Lichti Kaiser K, Xu C, Staudinger J. Cyclic AMP-dependent protein kinase signaling modulates pregnane x receptor activity in a species-specific manner. J Biol Chem. 2009;284:6639-49 pubmed publisher
    b>Pregnane x receptor is a ligand-activated transcription factor that regulates drug-inducible expression of several key cytochrome P450 enzymes and drug transporter proteins in liver and intestine in a species-specific manner...
  54. Braeuning A, Gavrilov A, Brown S, Wolf C, Henderson C, Schwarz M. Phenobarbital-mediated tumor promotion in transgenic mice with humanized CAR and PXR. Toxicol Sci. 2014;140:259-70 pubmed publisher
    The nuclear receptors CAR (constitutive androstane receptor) and possibly PXR (pregnane X receptor) mediate the hepatic effects of phenobarbital (PB) and similar-acting compounds...
  55. Woolsey S, Beaton M, Mansell S, Leon Ponte M, Yu J, Pin C, et al. A Fibroblast Growth Factor 21-Pregnane X Receptor Pathway Downregulates Hepatic CYP3A4 in Nonalcoholic Fatty Liver Disease. Mol Pharmacol. 2016;90:437-46 pubmed publisher
    ..diet-induced simple hepatic steatosis and lipid-loaded Huh7 cells had reduced nuclear localization of the pregnane X receptor (PXR), a key transcriptional regulator of CYP3A4 Furthermore, decreased nuclear PXR was observed in mouse ..
  56. Kodama S, Shimura T, Kuribayashi H, Abe T, Yoshinari K. Pregnenolone 16?-carbonitrile ameliorates concanavalin A-induced liver injury in mice independent of the nuclear receptor PXR activation. Toxicol Lett. 2017;271:58-65 pubmed publisher
    The pregnane X receptor (PXR) is well-known as a key regulator of drug/xenobiotic clearance. Upon activation by ligand, PXR transcriptionally upregulates the expression of drug-metabolizing enzymes and drug transporters...
  57. Terc J, Hansen A, Alston L, Hirota S. Pregnane X receptor agonists enhance intestinal epithelial wound healing and repair of the intestinal barrier following the induction of experimental colitis. Eur J Pharm Sci. 2014;55:12-9 pubmed publisher
    ..In the current study we examined the role of the pregnane X receptor (PXR) in modulating the intestinal epithelial wound healing response...
  58. Hasegawa M, Kapelyukh Y, Tahara H, Seibler J, Rode A, Krueger S, et al. Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line. Mol Pharmacol. 2011;80:518-28 pubmed publisher
    ..further complicated by the fact that the predictability of the clinically common drug-drug interaction of pregnane X receptor (PXR)-mediated CYP3A4 induction by animal studies is limited as a result of marked species differences in ..
  59. Ross J, Plummer S, Rode A, Scheer N, Bower C, Vogel O, et al. Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo. Toxicol Sci. 2010;116:452-66 pubmed publisher
    ..The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes...
  60. Assem M, Schuetz E, Leggas M, Sun D, Yasuda K, Reid G, et al. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem. 2004;279:22250-7 pubmed
  61. Fraser D, Zumsteg A, Meyer U. Nuclear receptors constitutive androstane receptor and pregnane X receptor activate a drug-responsive enhancer of the murine 5-aminolevulinic acid synthase gene. J Biol Chem. 2003;278:39392-401 pubmed
    ..typical cytochrome P450 pan-inducers phenobarbital and metyrapone, as well as specific activators of the pregnane X receptor and the constitutive androstane receptor...
  62. Hurst C, Waxman D. Environmental phthalate monoesters activate pregnane X receptor-mediated transcription. Toxicol Appl Pharmacol. 2004;199:266-74 pubmed
    ..The present study investigates the effects of phthalates on the pregnane X receptor (PXR), which mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification...
  63. Krausova L, Stejskalova L, Wang H, Vrzal R, Dvorak Z, Mani S, et al. Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene. Biochem Pharmacol. 2011;82:1771-80 pubmed publisher
    ..the functions of several nuclear receptors involved in the regulation of hepatic metabolism, including pregnane X receptor (PXR), which is referred to as a "master regulator" of drug/xenobiotic metabolism...
  64. Finn R, Henderson C, Scott C, Wolf C. Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway. Biochem J. 2009;417:43-54 pubmed publisher
    ..by activation of the nuclear receptor CAR (constitutive androstane receptor) and, to a lesser degree, PXR (pregnane X receptor)...
  65. Cheng X, Klaassen C. Critical role of PPAR-alpha in perfluorooctanoic acid- and perfluorodecanoic acid-induced downregulation of Oatp uptake transporters in mouse livers. Toxicol Sci. 2008;106:37-45 pubmed publisher
    ..In conclusion, PFOA and PFDA decrease mouse liver uptake transporters primarily via activation of PPAR-alpha. ..
  66. Milona A, Owen B, van Mil S, Dormann D, Mataki C, Boudjelal M, et al. The normal mechanisms of pregnancy-induced liver growth are not maintained in mice lacking the bile acid sensor Fxr. Am J Physiol Gastrointest Liver Physiol. 2010;298:G151-8 pubmed publisher
    ..Understanding pregnancy-induced hepatocyte hypertrophy in mice could suggest mechanisms for safely increasing functional liver capacity in women during increased metabolic demand. ..
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