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

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

PROVIDER: PRJNA509891 | ENA |

REPOSITORIES: ENA

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

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).

2018-12-14 | GSE123803 | GEO

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

2018-12-14 | GSE123802 | GEO

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

2018-12-18 | GSE123963 | GEO

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

Project description:Comparison of target genes from the pregnane X receptor (Pxr) in the liver vs the intestine

| PRJNA509890 | ENA

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

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

| PRJNA510394 | ENA

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

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

| PRJNA509892 | ENA

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.

2023-03-20 | GSE147256 | GEO

Pregnane X-receptor (PXR/NR1I2) activity is a hallmark of cancer stem cells and drives post-treatment tumor recurrence in colon cancer

Project description:Post-treatment recurrence remains a major clinical challenge in colorectal cancer (CRC), and increasing evidence suggests that Cancer Stem Cells (CSCs) may mediate this process due to their enhanced resistance to conventional therapeutics. We hypothesized that the Pregnane-X receptor (PXR) may drive the chemoresistance of colorectal CSCs.. shRNA-mediated PXR down-regulation was used to analyze the role of PXR on self-renewal in the colorectal cancer cell Line LS174T. Expression and activity of PXR were quantified under conditions that promote Cancer Stem Cells (CSCs) enrichment. Conversely, CSC characterization was performed in cells enriched along their PXR activity level.

2016-08-01 | E-MTAB-3471 | biostudies-arrayexpress

Transcriptional profiling of C57BL-mice with humanized CAR/PXR or CAR/PXR-knockout treated with DCB and CPA

Project description:To investigate the role of the nuclear receptors CAR (constitutive androstane receptor) and PXR (Pregnane X receptor) in mediating the effects of non-genotoxic carcinogens, groups of mice humanised or deleted for CAR and PXR were treated with 1,4-Dichlorobenzene or cyproterone acetate for 3d and liver tissue harvested for expression profiling. Control groups were treated with appropriate vehicles.

2018-04-27 | GSE68365 | GEO

The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice

Project description:The gut microbiota-intestine-liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined. By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion in Pxr+/+ vs Pxr-/- C57Bl6/J mice revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis revealed that microbiota-PXR interaction controlled fatty-acid and xenobiotic metabolism. Antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in livers from Pxr+/+ but not Pxr-/- male mice. These findings identify PXR as a hepatic effector of sexually dimorphic responses to microbiota-derived signals and reveal a potential new mechanism for unexpected drug-drug or food-drug interactions.

2020-08-26 | GSE156837 | GEO

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