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: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:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress
Project description:Acute kidney injury (AKI) remains a major global healthcare problem and there is a need to develop human-based models to study AKI in vitro. Towards this goal, we have characterized induced pluripotent stem cell-derived human kidney organoids and their response to cisplatin, a chemotherapeutic drug that induces AKI and preferentially damages the proximal tubule. We found that a single treatment with 50 µM cisplatin induces HAVCR1 and CXCL8 expression, DNA damage (γH2AX) and cell death in the organoids in a dose-dependent manner but greatly impairs organoid viability. DNA damage was not specific to the proximal tubule but also affected the distal tubule and interstitial cell populations. This lack of specificity correlated with low expression of the proximal tubule-specific SLC22A2/OCT2 transporter for cisplatin. To improve viability, we developed a repeated low-dose regimen of 4x 5 µM cisplatin over 7 days and found this causing less toxicity while still inducing a robust AKI response that included secretion of known AKI biomarkers and inflammatory cytokines. This work validates the use of human kidney organoids to model aspects of AKI, with the potential to identify new AKI biomarkers and develop better therapies.
2020-02-29 | GSE145085 | GEO