Identification and Validation of Hub Genes in Drug Induced Acute Kidney Injury Basing on Integrated Transcriptomic Analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227970 | GEO | 2023/03/27
REPOSITORIES: GEO
Similar Datasets
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:Transcriptional profiling of mouse kidney tissue comparing control untreated mice with mice treated with cisplatin. The latter makes kidney failure. Goal was to identify the alterations of N6-methyladenosine (m6A) RNA profiles in cisplatin-induced acute kidney injury (AKI) in mice.
2021-07-06 | GSE165100 | GEO
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
Project description:Cisplatin is a potent chemotherapeutic drug widely used to treat cancers. Unfortunately, its overaccumulation in kidney proximal tubular cell (PTC) shuts down fatty acid oxidation, resulting in cell necrosis and acute kidney injury (AKI). Bismuth drugs have long been used to treat gastrointestinal tract disorder and Helicobacter pylori infection. Interestingly, bismuth drugs also mitigate cisplatin-induced AKI, but the underlying mechanism remains unknown. In this study, we found 50nM bismuth specifically reduces cisplatin-induced cell necrosis. Using multiomics and protein-small molecule interaction techniques, we identified mitochondrial protein ALKBH7 as a specific target of bismuth. And ALKBH7 is depleted upon bismuth treatment. Bismuth treatment and ALKBH7 knockdown shared a proteomic similarity in suppressing programmed necrosis and promoting fatty acid metabolism. By gene knockout and silencing, we showed ALKBH7 depletion indeed greatly mitigates cisplatin-induced cell necrosis. We further demonstrated bismuth specifically depletes renal ALKBH7, prevents cisplatin-induced AKI and greatly increases survival rate in mice. Overall, we conclude ALKBH7 is specific target of bismuth drugs, and ALKBH7 depletion suppresses cisplatin-induced PTC necrosis and prevents AKI by preserving fatty acid metabolism.
2024-07-30 | PXD054362 | iProX
Project description:Cisplatin-induced acute kidney injury (AKI) is one of the most common and severe side effects and can prevent the use of this important agent. Unfortunately, preventive or therapeutic tools to address cisplatin-induced AKI are lacking. Interestingly, in the last decades a row of preconditioning strategies that employ the activation of cellular stress resistance pathways have been shown to be promising approaches to protect from organ injury in rodent models. Here, we characterized both the protective potential and the underlying molecular patterns of two strategies – caloric restriction and hypoxic preconditioning – in mice treated with cisplatin.
2018-11-12 | GSE106993 | GEO
Project description:Vancomycin is commonly used as a first line empiric therapy for gram positive organisms such as resistant Staphylococcus species. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those targeting higher trough concentrations. The mechanism of injury in humans remains not well understood with recent evidence pointing to cast nephropathy. In this study, we investigate the protein contents of urinary exosomes in patients with VAN-AKI to further elucidate mechanisms of injury.
| MSV000086053 | MassIVE
Project description:We use bulk RNA sequencing of sorted cells to characterize the gene expression profiles of renal MHCII+/-D11b+F4/80hi cells 72 hours after cisplatin-induced acute kidney injury (AKI). F4/80hi cells are activated after cisplatin induced AKI and start to downregulate MHCII on transcriptional level. Downregulation of MHCII is probably caused by a downregulation/inhibition of its most important transcriptional activator Ciita
2020-01-31 | GSE135921 | GEO
Project description:We aimed to investigate the therapeutic effects and mechanisms of Yishen Jiangzhuo decoction (YSJZD) in a mouse model of cisplatin-induced acute kidney injury (AKI). The mice were divided into the NC, cisplatin, and cisplatin + YSJZD groups. A concentration-dependent effect of YSJZD on cisplatin-induced AKI was observed, and the optimal concentration for intervention was calculated. Changes in blood urea nitrogen and serum creatinine levels combined with hematoxylin & eosin and periodic acid-Schiff staining, and transmission electron microscopy observations indicated that YSJZD enhanced renal function, reduced pathological injury, and protected renal tubular epithelial cells in cisplatin-induced AKI mice. The results of the transcriptomic and enrichment analyses showed that the mechanisms of YSJZD may be associated with inflammation, oxidation, apoptosis, and the TNF signal pathway. Immunofluorescence, oxidative stress index, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and western blotting (WB) revealed that YSJZD downregulated apoptosis in the renal tissues of AKI mice, and further decreased the expression levels of p-p65, p-p38 MAPK, tumor necrosis factor -α, cleaved-caspase-3, and malondialdehyde, while increasing the levels of SIRT3, GSH, and SOD. Overall, the results showed that YSJZD could effectively abrogate cisplatin-induced AKI in mice through mechanisms primarily related to its anti-inflammatory, antioxidative, and antiapoptotic effects by inhibited the TNF signal pathway. YSJZD warrants further investigation as a clinical empirical prescription.
2024-04-06 | GSE262792 | GEO
Project description:Although vancomycin, which is frequently used to treat drug-resistant bacterial infections, induces acute kidney injury (AKI) with high frequency, the only effective treatment is discontinuation of the drug, so analysis of effective avoidance methods is urgently needed. In this study, the expression of mRNA in the kidney prepared from1/2 nephrectomized mice which injected vancomycyn was investigated.
2024-07-29 | GSE237186 | GEO
Project description:Background: The inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Methods: Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI 72 hours post injury. Data was processed using the Seurat package. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation in in vitro human LECs. Results: We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved in endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models were also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. Conclusions: In this study, we uncover lymphatic vessel structural features of captured populations and injury-induced genetic changes. We further determine LEC gene expression is altered between injury models. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.
2024-02-20 | GSE236199 | GEO