GEO accession GSE280478 is currently private and is scheduled to be released on Oct 25, 2025.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1178671 | ENA |
REPOSITORIES: ENA
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Project description:Alcohol-associated liver disease (ALD) results from excessive alcohol consumption and is more severe in females. The prenane X receptor (PXR), a xenobiotic nuclear receptor essential for toxin defense, has been implicated in ALD, but the underlying mechanisms remain unclear. Due to species differences in ligand specificty, humanized PXR (hPXR) mouse models are necessary to investigate its role in the sexual dimorphism of ALD in humans. Ethanol exposure caused the most severe hepatoxicity in female hPXR mice with microarray analysis identifying 442 genes uniquely regulated by ethanol in female hPXR mice, implicated with ethanol-induced liver damage.
2025-10-25 | GSE280478 | GEO
Project description:Drug-induced liver injury (DILI), especially acetaminophen overdose, is the leading cause of acute liver failure. Pregnane X receptor (PXR) is a nuclear receptor and the master regulator of drug metabolism. Aberrant activation of PXR plays a pathogenic role in the acetaminophen hepatotoxicity. Here, we aimed to examine the PXR S-nitrosylation (SNO) in response to acetaminophen. We found that PXR was S-nitrosylated in hepatocytes and the mouse livers after exposure to acetaminophen or S-nitrosoglutathione (GSNO). Mass-spectrometry and site-directed mutagenesis identified the cysteine 307 as the primary residue for SNO-modification. In hepatocytes, SNO suppressed both agonist (rifampicin and SR12813)-induced and constitutively active PXR (VP-PXR) activations. Furthermore, in acetaminophen overdosed mouse livers, PXR protein was decreased at the centrilobular regions overlapping with increased SNO. In PXR-deficient (PXR-/-) mice, replenishing the livers with the SNO-deficient PXR significantly aggravated hepatic necrosis and apoptosis, increased HMGB1 release, and exacerbated liver injury and inflammation. Particularly, we demonstrated that S-nitrosoglutathione reductase (GSNOR) inhibitor N6022 promoted hepatoprotection by increasing the levels of PXR S-nitrosylation. In conclusion, PXR is post-translationally modified by S-nitrosylation in hepatocytes in response to acetaminophen. This modification mitigated the acetaminophen-induced PXR hyperactivity. It may serve as a new target for therapeutical intervention.
2024-03-06 | GSE243679 | GEO
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
Project description:Ethanol Treatment Enhances Drought Stress Tolerance in Plants
| PRJNA832309 | ENA
Project description:Pregnane X Receptor (PXR) protects against cisplatin-induced acute kidney injury
| PRJNA613607 | ENA
Project description:We altered the NIAAA (Gao Binge Model) of 8 week chronic plus binge ethanol (E8G1) to have 3 total ethanol gavages (5 g/kg; 1 every 24h) of ethanol after 8 weeks of chronic ethanol feeding (E8G3) to determine how the liver responds to chronic plus consecutive binge ethanol. Surprisingly, E8G3 treatment induced lower levels of liver injury, steatosis, inflammation, and fibrosis as compared to mice after E8G1 treatment. Microarray analyses were performed, identifying several pathways that may contribute to the observed liver adaptation to binge ethanol. In addition, cytochrome P450 2B10 (Cyp2b10) was a top upregulated gene in the E8G1 group and further upregulated in the E8G3 group, but only moderately induced after chronic ethanol consumption, which was confirmed by RT-qPCR and western blot analyses. Genetic disruption of the Cyp2b10 gene worsened liver injury in E8G1 and E8G3 mice with higher blood ethanol levels compared to wild-type control mice, while in vitro experimentation revealed that CYP2b10 did not directly promote ethanol metabolism. Metabolomic analyses revealed significant differences in hepatic metabolites from E8G1-treated Cyp2b10 KO and WT mice, and these metabolic alterations may contribute to the reduced liver injury in Cyp2b10 KO mice.
2022-09-07 | GSE212755 | GEO
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
Project description:Ethanol treatment enhances drought stress avoidance in cassava (Manihot esculenta Crantz)
| PRJNA801047 | ENA
Project description:Gene expression profiles of ethanol treated drought-stressed roots and shoots was performed at 3, 24, and 72 h after ethanol treatment and 1, 3, and 5 days after drought stress were analyzed using the custom microarray Agilent-034592.
2022-10-04 | GSE201609 | GEO
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