Gene expression profiles in isolated proximal tubules and whole kidneys of rats after cisplatin-administration
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE37133 | GEO | 2013/12/24
SECONDARY ACCESSION(S): PRJNA158411
REPOSITORIES: GEO
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Project description:To clarify the effects of cisplatin (cis-diamminedichloroplatinum II, CDDP) on the gene expression profiles in renal proximal tubules, microarray analyses were carried out using total RNA samples isolated from microdissected proximal tubules and whole kidneys. The molecular events underlying acute kidney injury (AKI) in the proximal tubules of rats with cisplatin-induced nephrotoxicity were successfully clarified with 17,000 transcripts. Renal proximal tubules were isolated under microscopy, and transcriptome data were collected with Rat Genome Survey Microarray® (Applied Biosystems)
2013-12-24 | E-GEOD-37133 | biostudies-arrayexpress
Project description:This study was aimed to investigate the role and underlying mechanism of TRPM2 in cisplatin nephrotoxicity. Cisplatin-induced acute kidney injury (AKI) model was established in WT and TRPM2-KO mice. The transcriptome profiling of the kidneys of WT and TRPM2-KO mice treated with cisplatin was compared to find differentially expressed gene which may be related to TRPM2 on cisplatin nephrotoxicity.
2023-03-30 | GSE203584 | GEO
Project description:Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK in vivo and in vitro. Furthermore, we confirmed that smgGDS deficiency aggravated apoptosis and ER stress in vivo and in vitro. And the ER stress inhibitor 4-Phenylbutyric acid and the inhibition of PERK phosphorylation mitigated smgGDS deficiency-induced ER stress related apoptosis following cisplatin treatment, while the eIF2α phosphorylation inhibitor could not reverse the smgGDS deficiency accelerated cell death. Furthermore, the over-expression of smgGDS could reverse the ER stress and apoptosis caused by CDDP. Overall, smgGDS regulated PERK-dependent ER stress and apoptosis, thereby influencing renal damage. This study identified a target for diagnosing and treating cisplatin-induced acute kidney injury.
2024-09-13 | GSE275317 | GEO
Project description:Acute kidney injury and nephrotoxicity are important clinical side effects of cisplatin. Thus, the mechanisms of this disease, and potential treatment options are important to understand in their entity. Here, we analyzed the proteome of cisplatin induced acute kidney injury in a mouse model. Functionally we found that calorie restriction was able to completely blunt Cisplatin induced AKI, and hypoxia ameliorated cCisplatin induced AKI. To investigate the mechanism for this in high throughput, we performed label-free single-shot proteomic analyses of these kidneys.Acute kidney injury and nephrotoxicity are important clinical side effects of cisplatin. Thus, the mechanisms of this disease, and potential treatment options are important to understand in their entity. Here, we analyzed the proteome of cisplatin induced acute kidney injury in a mouse model. Functionally we found that calorie restriction was able to completely blunt Cisplatin induced AKI, and hypoxia ameliorated cCisplatin induced AKI. To investigate the mechanism for this in high throughput, we performed label-free single-shot proteomic analyses of these kidneys.
2020-01-30 | PXD005525 | Pride
Project description:This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determined differential mRNA and miRNA expression between A549/DDP and A549 cells
2021-05-31 | GSE157692 | GEO
Project description:Objective: Cisplatin (CDDP) has been widely used for chemotherapy against tumours. However，the nephrotoxicity has limited its clinical use. Here, we reported a novel compound, Capilliposide A (CPS-A), to exhibit therapeutic effects on CDDP-induced acute kidney injury （AKI）and explored its potential mechanisms via transcriptome and metabolome. Materials and methods: HK-2 cells were treated with CPS-A, after which cell viability, apoptosis and inflammation were investigated. A mouse model of AKI was constructed by single injection of CDDP in vivo. The renal function and morphology and mitochondrial function were assessed by pathological section and transmission electron microscope (TEM). Transcriptomics and metabolomics are used to explore possible mechanisms which was later verified in vitro. Results: CPS-A administration improved the survival rates of HK-2 cells with a significant decrease in the expression of KIM-1, NGAL, IL-6, IL-8 and IL-1β. In vivo results also suggested that CPS-A attenuates CDDP-induced kidney injury by reducing serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Furthermore, TEM also showed the improvement of mitochondrial ultrastructure both in vivo and vitro. Transcriptomics analysis of the mice's renal cortex indicated the expression of ATF4 and CHOP were upregulated, which was further validated by qPCR and Western blotting in vitro. Integrative analysis of transcriptome and metabolome indicated that L-Leucine enriched in Valine, leucine and isoleucine degradation might be potential targets. Conclusions: CPS-A can effectively regulate endogenous metabolites associated with amino acid metabolism and ameliorate apoptosis and oxidative stress in CDDP-induced AKI by reducing endoplasmic reticulum stress.
2023-10-31 | GSE246133 | GEO
Project description:We investigated an acute kidney injury (AKI) model in rats induced by cisplatin (Cp) administration. The cisplatin is widely used since its biochemical and histopathological characteristics are representative of drug-induced AKI in humans. Male Wistar rats were dosed once ip with 0, 1 and 3 mg/kg cisplatin. Tubular necorsis was observed histopathologically in all treated rats and war recovery on day 26. Gene expression profiling of the kidney cortex with microarrays 3, 5, 8, and 26 days after single administration of 3mg/kg Cp revealed a major profile pattern characterized by maximally increased and decreased mRNA levels on day 8, with clear changes already found 3 days after treatment for about half of the mRNAs. The mRNA expression pattern after administration of 1mg/kg Cp was overall similar, yet with a dose-dependent smaller fold-change. In summary we found 274 mRNAs showing significantly altered levels in the kidney of which 162 were increased and 112 decreased, respectively. Functional interpretation of the proteins encoded by these mRNAs revealed induction of a DNA damage response likely caused by the known molecular activity of Cp as DNA alkylating agent. Increased mRNAs associated with apoptosis (encoded by the corresponding genes like B-cell lymphoma 3-encoded protein, Bcl3; mouse double minute 2 homolog, Mdm2; p21/WAF1 also known as cyclin-dependent kinase inhibitor 1), cell cycle regulation (encoded by the corresponding genes like Cyclin-G1, Ccng1; B-cell translocation gene 2, Btg2) and stress response may have partly been induced by the DNA damage, but also by the kidney damage associated with Cp administration. Increased levels of mRNAs indicating regeneration (encoded by the corresponding genes like SPARC- related modular calcium-binding protein 2, Smoc2; Tenascin C, Tnc) and decreased levels of mRNAs coding for proteins related to kidney function, indicating dedifferentiation, are likely related to the observed kidney injury. Male Han Wistar rats (8 weeks old) were randomly grouped (n = 6) and dosed once i.p. with 0, 1 or 3 mg/kg body weight cis-diamminedichloroplatinum (II) (cisplatin; Sigma Aldrich, Germany) diluted in 0.9% saline. For histopathological examination of the kidney and for kidney RNA isolation animals were euthanized on days 3, 5, 8 and 26.
2016-08-23 | E-GEOD-85957 | biostudies-arrayexpress
Project description:Acute kidney injury (AKI) have been thought to be reversible condition, however, emerging evidence demonstrated association between AKI and subsequent development of irreversible fibrosis and chronic kidney disease. In the present study, since recovery of AKI depends on renal tubular regeneration, factors expressing in renal tubules in adaptive or maladaptive repair process were investigated to predict reversibility of kidney injury. In the kidney of female F344 rats subjected to ischemia/reperfusion (I/R), regenerative tubules and dilated tubules were observed at 3 and 7 days after I/R. In fibrotic areas of the kidney of male SD rats subjected to I/R, renal tubules were dilated or atrophied. From microarray data of regenerative tubules, survivin, sex-determining region Y (SRY)-box 9 (SOX9), and CD44 were extracted as factors possibly relating to tubular regeneration or fibrosis. Immunohistochmical analysis demonstrated that survivin and SOX9 expressed in regenerative tubules, while SOX9 also expressed in renal tubules in fibrotic area, indicating that survivin and SOX9 contribute renal tubular regeneration, but sustained SOX9 expression may lead fibrosis. CD44 expressed in dilated tubules at day 3 and 7, and tubules in fibrotic area, suggesting that CD44 expressed in maladaptive tubules. These information will be helpful to consider reversibility of kidney injury.
2020-06-01 | GSE148420 | GEO
Project description:dB/dB mice develop different kidney pathologies resulting from high body weight. We seek to better understand the mechanisms of this kidney damage in proximal tubules. We isolated RNA from proximal tubules of different groups of mice, and we seek to understand how the anti-oxidant enzyme catalase may regulate kidney damage in this model.
2009-12-24 | GSE19640 | GEO
Project description:The transcriptional response to CDDP of three ovarian cancer cell lines was studied. These lines show different genetic profiles and display different susceptibilities to CDDP. The time and doses that resulted in the apoptotic death of each cell line was identified and used to study the expression profiles associated to CDDP-induced cell death in each cell line. CDDP: cis-diamminedichloroplatinum(II)
2013-12-31 | GSE38545 | GEO