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

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

PROVIDER: PRJNA613607 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11356224_1.fastq.gz	Fastqsanger.gz
	SRR11356224_2.fastq.gz	Fastqsanger.gz
	SRR11356225_1.fastq.gz	Fastqsanger.gz
	SRR11356225_2.fastq.gz	Fastqsanger.gz
	SRR11356226_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

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

Pregnane X receptor knockout mice display aging-dependent wearing of articular cartilage

Project description:Steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and the intestine. They function as xenobiotic sensors by inducing genes involved in detoxification and drug excretion. Recent evidence showed that SXR and PXR are also expressed in bone tissue where they mediate bone metabolism. Here we report that systemic deletion of PXR results in aging-dependent wearing of articular cartilage of knee joints. Histomorphometrical analysis showed remarkable reduction of width and an enlarged gap between femoral and tibial articular cartilage in PXR knockout mice. We hypothesized that genes induced by SXR in chondrocytes have a protective effect on articular cartilage and identified Fam20a (family with sequence similarity 20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and vitamin K2. Lastly, we demonstrated the biological significance of Fam20a expression in chondrocytes by evaluating osteoarthritis-related gene expression of primary articular chondrocytes. Consistent with epidemiological findings, our findings indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging.

2015-03-31 | GSE60401 | GEO

Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney]

Project description:Cisplatin is a potent chemotherapeutic drug, widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, such as nephrotoxicity and chemotherapy-induced peripheral neuropathy. Therefore, there is an urgent medical need to identify novel strategies that would limit cisplatin-induced toxicity. In the present study, we provide evidence that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) significantly protects from cisplatin-induced nephrotoxicity and neuropathic pain in experimental models of acute and sub-chronic cisplatin intoxication. Importantly, we also demonstrate that the anti-tumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and even potentiated at the molecular level. Altogether, the present results support the use of istradefylline as a new valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.

2022-09-12 | GSE179245 | GEO

Pregnane X receptor knockout mice display aging-dependent wearing of articular cartilage

2015-03-31 | E-GEOD-60401 | biostudies-arrayexpress

A Novel Statistical Algorithm for Gene Expression Analysis Differentiates PXR-Dependent and Independent Mechanisms of Toxicity

Project description:The objective of the present study is to examine the potential role of the pregnane x receptor (PXR) in mice treated with an small molecule inhibitor for beta-secretase (CMP013) Two groups of mice, C57Bl/6 (PXR+/+) and PXR-knockout C57Bl/6NTac (PXR-/-), were administered either CMP013 or vehicle. There were five animals per treatment group for each strain. After 96 h, all animals were euthanized, and liver samples were collected for RNA. extraction.

2010-08-25 | E-GEOD-23780 | biostudies-arrayexpress

A Novel Statistical Algorithm for Gene Expression Analysis Differentiates PXR-Dependent and Independent Mechanisms of Toxicity

2010-08-25 | GSE23780 | GEO

Transcriptional profiling of liver from wild type and PXR-null mice treated with PCN

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

Transcriptional profiling of Primary Human Hepatocytes (PHH) depleted for PXR and treated with CITCO or Phenobarbital in -/+EGF medium

Project description:In primary human hepatocytes (PHH) the involvement of the Pregnane X Receptor (PXR) in genes regulations by Phenobarbital (PB) has never been evaluated at the transcriptomic level. Here we investigated the impact of PXR depletion and epidermal growth factor on PXR dependent gene modulation by PB in PHH. The potential crosstalk with CAR was investigated using Phenobarbital and the direct CAR activator (CITCO) in presence or in absence of EGF.

2018-04-27 | GSE68495 | GEO

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