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Series GSE147256 Query DataSets for GSE147256
Status Public on Mar 20, 2023
Title Pregnane X Receptor (PXR) protects against cisplatin-induced acute kidney injury
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design Renal mRNA profiles of 8-week old wild type (WT) treated with or without cisplatin and/or PCN were generated by deep sequencing, in triplicate, using Illumina platform.
 
Contributor(s) Luan Z, Guan Y
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Mar 20, 2020
Last update date Mar 20, 2023
Contact name Zhilin Luan
E-mail(s) zhilin_luan@sina.com
Phone +8641186118982
Organization name Advanced Institute for Medical Sciences, Dalian Medical University
Street address 9 W., S. Lvshun Blvd.
City Dalian
State/province China
ZIP/Postal code 116044
Country China
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (12)
GSM4422820 Control1: Control rep1
GSM4422821 Control2: Control rep2
GSM4422822 Control3: Control rep3
Relations
BioProject PRJNA613607
SRA SRP253439

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE147256_gene_fpkm.txt.gz 4.3 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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