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Comparison of target genes from the pregnane X receptor (Pxr) in the liver vs the intestine [ileum]

ABSTRACT: We performed a transcriptomic comparison of the Pxr-regulated genes in the liver and intestine (ileum and colon) using microarrays in adult wild-type (WT) vs Pxr-/- C57Bl6/J male mice treated with the rodent specific Pxr ligand pregnenolone 16α-carbonitrile (PCN) (100 mg/kg i.p. once daily for 4 days).

ORGANISM(S): Mus musculus

PROVIDER: GSE123803 | GEO | 2018/12/14

REPOSITORIES: GEO

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Comparison of target genes from the pregnane X receptor (Pxr) in the liver vs the intestine [colon]

Project description:We performed a transcriptomic comparison of the Pxr-regulated genes in the liver and intestine (ileum and colon) using microarrays in adult wild-type (WT) vs Pxr-/- C57Bl6/J male mice treated with the rodent specific Pxr ligand pregnenolone 16α-carbonitrile (PCN) (100 mg/kg i.p. once daily for 4 days).

2018-12-18 | GSE123963 | GEO

Comparison of target genes from the pregnane X receptor (Pxr) in the liver vs the intestine [liver]

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The effect of PCN on gene expression in mouse primary hepatocytes

Project description:The effect of prototypical pregnane receptor X (PXR) agonist (pregnenolone 16α-carbonitrile) PCN on hepatic gene expression was studied in mice primary hepatocytes.

2018-01-22 | GSE106293 | GEO

Effect of PCN on CAR and PXR regulated genes involved in circadian rhythm, drug metabolism and cholesterol homeostasis

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

Pregnane X Receptor (PXR) protects against cisplatin-induced acute kidney injury

Project description:Background: Cisplatin-induced acute kidney injury (CAKI) has been recognized as one of the most serious side effects of cisplatin. Pregnane X receptor (PXR) is a ligand-dependent nuclear receptor and serves as a master regulator of xenobiotic detoxification. Increasing evidence also suggests PXR has many nonxenobiotic functions including the regulation of cell proliferation, inflammatory response and glucose and lipid metabolism. Methods: In this study, we aimed to investigate the role of PXR in cisplatin-induced nephrotoxicity. CAKI model was performed in wild-type or PXR knockout mice. Pregnenolone 16α-carbonitrile (PCN), a mouse PXR specific agonist, was used for PXR activation. The renal function, biochemical, histopathological and molecular alterations were examined in mouse blood, urine or renal tissues. Whole transcriptome analysis was performed by RNA sequencing. Dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays were applied to determine the regulation of PXR on its target genes. Results: We found that PXR activation significantly attenuated CAKI as reflected by improved renal function, reduced renal tubular apoptosis, ameliorated oxidative and endoplasmic reticulum stress, and suppressed inflammatory factor expression. RNA sequencing analysis revealed that the renoprotective effect of PXR was associated with multiple crucial signaling pathways. In particular, PXR protected against cisplatin-induced AKI by the activation of PI3K/AKT pathway and the induction of multidrug and toxin extrusion 1 (MATE1), an important transporter mediating cellular excretion of cisplatin, in the kidney. Conclusions: Our results demonstrate that PXR activation can preserve renal function in cisplatin-induced AKI and suggest a possibility of PXR as a novel therapeutic target for cisplatin-induced nephrotoxicity.

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Project description:The mice were treated i.p. with pregnenolone-16-α-carbonitrile (PCN, 50mg/kg dissolved in DMSO-corn oil 1:3) or vehicle (DMSO-corn oil 1:3) once daily for four days. The mice were fasted for four hours and then administered glucose (2g/kg) by oral gavage or further kept on fasting. The mice were sacrificed 1 hour after glucose administration.

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Effect of PCN on CAR and PXR regulated genes involved in circadian rhythm, drug metabolism and cholesterol homeostasis

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RNA-seq analysis of mouse liver transcriptome following exposure to TCPOBOP or PCN

Project description:Changes in gene expression were assayed in mouse liver nuclear RNA following a single injection of the CAR agonist TCPOBOP (1,4-Bis-[2-(3,5-dichloropyridyloxy)]benzene) or the PXR agonist PCN (pregnenolone 16α-carbonitrile) in 7-week old mice. This study is part of a larger study entitled Sex-Differential Responses of Tumor Promotion-Associated Genes and Dysregulation of Novel Long Noncoding RNAs in Constitutive Androstane Receptor-Activated Mouse Liver (PMID: 28903501).

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Gene expression analysis in rat liver after exposure to pregnenolone-16α-carbonitrile

Project description:RCCHanTM:WIST male rats were administered for 7 days by oral gavage with vehicle (corn oil) or 100 mg/kg/day of pregnenolone-16α-carbonitrile(PCN). We used microarrays to evaluate gene expression profiling in rat liver at the early phase of treatment with PCN.

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Transcriptomic effect of high-fat diet and PCN treatment on the gonadal white adipose tissue of C57BL/6N mice.

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.

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