Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA286100 | ENA |
REPOSITORIES: ENA
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Project description:Cisplatin induces both acute and chronic nephrotoxicity during chemotherapy in cancer patients. Here, we report the study of single-nucleus sequencing (snRNA-seq) of cisplatin-induced nephrotoxicity.
2023-08-05 | GSE239749 | GEO
Project description:Cisplatin is a potent chemotherapeutic drug, widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, such as nephrotoxicity and chemotherapy-induced peripheral neuropathy. Therefore, there is an urgent medical need to identify novel strategies that would limit cisplatin-induced toxicity. In the present study, we provide evidence that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) significantly protects from cisplatin-induced nephrotoxicity and neuropathic pain in experimental models of acute and sub-chronic cisplatin intoxication. Importantly, we also demonstrate that the anti-tumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and even potentiated at the molecular level. Altogether, the present results support the use of istradefylline as a new valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.
2022-09-12 | GSE179246 | GEO
Project description:Cisplatin is a potent chemotherapeutic drug, widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, such as nephrotoxicity and chemotherapy-induced peripheral neuropathy. Therefore, there is an urgent medical need to identify novel strategies that would limit cisplatin-induced toxicity. In the present study, we provide evidence that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) significantly protects from cisplatin-induced nephrotoxicity and neuropathic pain in experimental models of acute and sub-chronic cisplatin intoxication. Importantly, we also demonstrate that the anti-tumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and even potentiated at the molecular level. Altogether, the present results support the use of istradefylline as a new valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.
2022-09-12 | GSE179245 | GEO
Project description:The cellular and molecular mechanisms by which cisplatin induces nephrotoxicity have been investigated extensively. However, the role of long non-coding RNAs (lncRNAs) in cisplatin-induced nephrotoxicity has not been received much attention. Here, we explore the functions and underlying mechanisms of a novel lncRNA XLOC_032768 in cisplatin-induced nephrotoxicity. Cisplatin treatment resulted in the apoptosis of renal epithelial cells in a mouse model and human renal proximal tubular epithelial cells (HK-2). By performing differentially expressed genes (DEGs) of the transcriptome data, we found the expression of lncRNA XLOC_032768 was significantly repressed by cisplatin treatment, which was also validated by RT-qPCR experiment of in vivo and in vitro model. Overexpression of lncRNA XLOC_032768 significantly inhibited the cisplatin-induced apoptosis of HK-2 and the expression of biomarkers for cisplatin-induced nephrotoxicity. Results from XLOC_032768 overexpression experiment revealed that XLOC_032768 target the tumor necrosis factor (TNF)-α in trans in HK-2 cells and mouse exposed to cisplatin. The administration of lncRNA XLOC_032768 attenuated renal dysfunction, morphological damage, and renal tubular cell injury, which was accompanied by TNF-α preservation, in a mouse model of cisplatin nephrotoxicity. These data indicate that XLOC_032768 suppressed cisplatin-induced apoptosis of tubular epithelial cells and acute kidney injury via a TNF mechanism. LncRNA XLOC_032768 would be a novel agent to reduce cisplatin-induced nephrotoxicity.
2021-07-27 | GSE142137 | GEO
Project description:The cellular and molecular mechanisms by which cisplatin induces nephrotoxicity have been investigated extensively. However, the role of long non-coding RNAs (lncRNAs) in cisplatin-induced nephrotoxicity has not been received much attention. Here, we explore the functions and underlying mechanisms of a novel lncRNA XLOC_032768 in cisplatin-induced nephrotoxicity. Cisplatin treatment resulted in the apoptosis of renal epithelial cells in a mouse model and human renal proximal tubular epithelial cells (HK-2). By performing differentially expressed genes (DEGs) of the transcriptome data, we found the expression of lncRNA XLOC_032768 was significantly repressed by cisplatin treatment, which was also validated by RT-qPCR experiment of in vivo and in vitro model. Overexpression of lncRNA XLOC_032768 significantly inhibited the cisplatin-induced apoptosis of HK-2 and the expression of biomarkers for cisplatin-induced nephrotoxicity. Results from XLOC_032768 overexpression experiment revealed that XLOC_032768 target the tumor necrosis factor (TNF)-α in trans in HK-2 cells and mouse exposed to cisplatin. The administration of lncRNA XLOC_032768 attenuated renal dysfunction, morphological damage, and renal tubular cell injury, which was accompanied by TNF-α preservation, in a mouse model of cisplatin nephrotoxicity. These data indicate that XLOC_032768 suppressed cisplatin-induced apoptosis of tubular epithelial cells and acute kidney injury via a TNF mechanism. LncRNA XLOC_032768 would be a novel agent to reduce cisplatin-induced nephrotoxicity.
2021-07-27 | GSE142134 | GEO
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:The kidney plays a critical role in fluid homeostasis, glucose control, and drug excretion. Loss of kidney function due to drug-induced nephrotoxicity affects over 20% of the adult population. The kidney proximal tubule is a complex vascularized structure that particularly vulnerable to drug-induced nephrotoxicity. Here we introduce a model of vascularized human kidney organoids with integrated tissue embedded micro-sensors for oxygen, glucose, lactate and glutamine, providing real time assessment of cellular metabolism. Our model shows that both the immunosuppressive drug cyclosporin (Neoral®) and the anti-cancer drug cisplatin (Platinol®) disrupt proximal tubule polarity at sub-toxic concentrations, leading to glucose accumulation and lipotoxicity. Impeding glucose reabsorption using glucose transport inhibitors blocked cyclosporin and cisplatin toxicity by 1,000 to 10-folds, respectively. Retrospective study of 247 patients receiving cyclosporin or cisplatin in combination with the SGLT-2 inhibitor gliflozin showed significant reduction in creatinine and uric acid recognized markers of kidney damage. These results demonstrate the potential of sensor-integrated organoid-on-chip platforms to elucidate new mechanisms of action and rapidly reformulate effective therapeutic solutions, increasing drug safety and reducing the cost of clinical and commercial failures.
2020-03-31 | GSE147735 | GEO
Project description:Chronic kidney disease (CKD) complicates cisplatin-based chemotherapy of cancer patients. Here we investigate microRNA (miRNA)-regulated transcriptomic activity to unveil biological processes associated with cisplatin-induced kidney injury. Implementing chimeric-eCLIP-seq approach to a mouse model for cisplatin-induced CKD, we identify direct pairs of miRNA and their target messenger RNA in the injured kidney. We find a dedicated transcriptomic program directed by a group of miRNAs that alter metabolic pathways centered on mitochondria in the injured kidneys. Specifically, cisplatin-induced miRNA, miR-429-3p suppresses the mitochondria pathway that catalyzes branched-chain amino acid (BCAA), eventually leading to lipid peroxidation-dependent cell death, called ferroptosis. Thus, the identification of miRNA-429-3p-mediated stimulation of ferroptosis suggests a therapeutic potential for BCAA pathway modulation in ameliorating CKD and cisplatin-associated nephrotoxicity.
2023-11-01 | GSE242808 | GEO
Project description:Chronic kidney disease (CKD) complicates cisplatin-based chemotherapy of cancer patients. Here we investigate microRNA (miRNA)-regulated transcriptomic activity to unveil biological processes associated with cisplatin-induced kidney injury. Implementing chimeric-eCLIP-seq approach to a mouse model for cisplatin-induced CKD, we identify direct pairs of miRNA and their target messenger RNA in the injured kidney. We find a dedicated transcriptomic program directed by a group of miRNAs that alter metabolic pathways centered on mitochondria in the injured kidneys. Specifically, cisplatin-induced miRNA, miR-429-3p suppresses the mitochondria pathway that catalyzes branched-chain amino acid (BCAA), eventually leading to lipid peroxidation-dependent cell death, called ferroptosis. Thus, the identification of miRNA-429-3p-mediated stimulation of ferroptosis suggests a therapeutic potential for BCAA pathway modulation in ameliorating CKD and cisplatin-associated nephrotoxicity.
2023-11-01 | GSE242807 | GEO