Transcriptomic effect of high-fat diet and PCN treatment on the livers of of PXR deficient mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE162196 | GEO | 2023/09/22
REPOSITORIES: GEO
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Project description:C57BL/7N mice were fed high-fat diet (HFD) and treated with Pregnenolone-16alfa-carbonitrile (PCN), a selective murine PXR agonist, and duodenal effects of the high-fat diet feeding and PCN treatment were studied.
2023-09-22 | GSE163407 | GEO
Project description:C57BL/7N mice were fed high-fat diet (HFD) and treated with Pregnenolone-16alfa-carbonitrile (PCN), a selective murine PXR agonist, and duodenal effects of the high-fat diet feeding and PCN treatment were studied.
2023-09-22 | GSE168196 | GEO
Project description:C57BL/7N mice were fed high-fat diet (HFD) and treated with Pregnenolone-16alfa-carbonitrile (PCN), a selective murine PXR agonist, and duodenal effects of the high-fat diet feeding and PCN treatment were studied.
2023-09-22 | GSE168197 | GEO
Project description:The nuclear receptor PXR (Pregnane X rreceptor) mediates the effects of pregnenolone-16alpha-carbonitrile (PCN) on gene transcription. The relative role of PXR and also CAR to the induction response by PCN was studied on cDNA arrays containing 320 (Steroltalk V2) genes (genes involved in cyrcadian rhythm, drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PCN for gene expression within the European Framework V program âSteroltalkâ (www.steroltalk.net). Results from these experiments show the complex role of PXR receptor in the expression of genes involved in cyrcadian rhythm, drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 40mg/kg PCN or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the PCN treated ones and hybridized to Steroltalk V2 arrays.
2010-05-16 | E-GEOD-12537 | biostudies-arrayexpress
Project description:The nuclear receptor PXR (Pregnane X rreceptor) mediates the effects of pregnenolone-16alpha-carbonitrile (PCN) on gene transcription. The relative role of PXR and also CAR to the induction response by PCN was studied on cDNA arrays containing 320 (Steroltalk V2) genes (genes involved in cyrcadian rhythm, drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PCN for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments show the complex role of PXR receptor in the expression of genes involved in cyrcadian rhythm, drug metabolism and cholesterol biosynthesis.
2008-11-13 | GSE12537 | GEO
Project description:Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR). PXR controls the expression of a large battery of genes involved in xenobiotic metabolism. Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions. Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist.
2014-09-30 | GSE55746 | GEO
Project description:PCN, a selective murine PXR agonist, was administered to obese mice with the goal to investigate what transcriptional changes PXR activation cause in the livers of obese mice.
2021-08-06 | GSE136667 | GEO
Project description:Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR). PXR controls the expression of a large battery of genes involved in xenobiotic metabolism. Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions. Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist. The animal studies were carried out at the University of Kansas Medical Center (Kansas City, KS) under federal guidelines for the use and care of laboratory animals and was approved by the KUMC Institutional Animal Care and Use Committee. Eight-week-old adult C57BL/6 mice were purchased from Jackson Laboratories (Bar Harbor, ME). Generation of the PXR-null mice was previously described (Staudinger et al., (2001), Proc Natl Acad Sci USA 98:3369M-bM-^@M-^S3374). PXR-null breeder pairs were engineered and backcrossed into the C57BL/6 background. Adult male wild-type mice and PXR-null mice were maintained on standard laboratory chow and were allowed food and water ad libitum. All mice were treated once a day i.p. with either vehicle (corn oil) or PCN at 400 mg/kg/day for 4 days. Livers were removed 24-hrs after the last dose. Portions of the livers were rapidly snap-frozen in liquid nitrogen and stored at -70M-BM-0C until analysis. Liver gene expression analysis was performed according to the Affymetrix recommended protocol using Affymetrix Mouse Genome 430 2.0 GeneChipsM-BM-.. Total RNA (5 M-NM-<g per sample) was labelled using the AffymetrixM-BM-. One-Cycle cDNA Synthesis protocol and hybridized to arrays as described by the manufacturer (AffymetrixM-BM-., Santa Clara, CA). Microarray hybridizations were conducted overnight at 45M-BM-0C while rotating in an Affymetrix hybridization oven. After 16 hours of hybridization, the cocktail was removed and the arrays were washed and stained in an Affymetrix GeneChipM-BM-. fluidics station 450 according to the Affymetrix-recommended protocol. Arrays were scanned on an Affymetrix GeneChipM-BM-. scanner. Four mice per group were examined.
2014-09-30 | E-GEOD-55746 | biostudies-arrayexpress
Project description:TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) and PCN (pregnenolone 16α-carbonitrile) are inducers of drug metabolism through activation of nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor), respectively. Mouse experiment was designed to study the effect of CAR and PXR activation on cholesterol homeostasis genes and other genes, which are present on the Steroltalk v2 microarray. Treatments were combined with standard and high-cholesterol diet to observe the interference of high liver cholesterol on nuclear receptor transcription regulation. All experiments were done within the European sixth Framework program âSteroltalkâ (www.steroltalk.net). Results form these experiments give new knowledge about involvement of âxenosensorsâ CAR and PXR in regulation of endogenous liver metabolism. Animals were injected i.p. 3mg/kg TCPOBOP, 40 mg/kg PCN or vehicle (corn oil) in combination of one week of standard or 1% cholesterol diet prior tretament. After 24h they were sacrificed and total RNA was isolated from the livers. Each sample was hybridized with a reference sample to Steroltalk v2 microarrays.
2010-10-08 | E-GEOD-13688 | biostudies-arrayexpress
Project description:Purpose: To explore the role of PXR signaling in regulating macrophage transcriptome related to atherogenesis Methods: Peritoneal macrophages were isolated from LDLR knockout mice with myeloid specific PXR deficiency (PXRΔMyeLDLR-/-) and their littermates (PXRF/FLDLR-/-). Then the macrophages were treated with a PXR ligand PCN or DMSO control for 12 hr. Total RNA was extracted for RNAseq Results: PCN-mediated PXR activation induced 439 differentially expressed genes (DEGs) with false discovery rate (FDR) < 5% and fold change >1.5 in control macrophages. By contrast, PCN only induced 38 DEFs in PXR-deficient macrophages. Conclusions: These results indicate that PXR signaling may affect many genes in macrophages related atherosclerosis development.
2020-02-22 | GSE145719 | GEO