Similar Datasets
Project description:Characteristics of the senescent cells of the chronic kidney disease in mice
| PRJNA874739 | ENA
Project description:In this study, isobaric tags for relative and absolute quantification (ITRAQ) and Q Exactive mass spectrometer were used for non-targeted proteomic profiling of forearm arteries and veins in patients with chronic kidney disease stage 5 (with or without diabetes mellitus, obtained from arteriovenous fistula surgery) and healthy controls (obtained from patients with forearm trauma). Protein identifications were acquired against the Uniport Human database. As a result, 497609 spectra were obtained and 3244 proteins were identified with 96525 matched peptides.
2019-06-24 | PXD010883 | Pride
Project description:The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Notably, hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan. Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease due to its well-documented connection with aging and senescence. Herein, a prospective cohort study revealed that LOY in blood is associated with an increased incidence of kidney diseases. Analyses of transcriptional signatures in human kidneys found that immune cell LOY is enriched in patients with kidney disease and associated with greater levels of cellular senescence. In mice, hematopoietic LOY led to renal dysfunction that was accompanied by senescent cell accumulation in models of kidney injury and advanced age. Accordingly, treatment with a senolytic agent promoted senolysis and preferentially inhibited the progression of renal dysfunction in LOY mice. The hematopoietic LOY condition led to the upregulation of multiple immune inhibitory receptors. Treatment with the combination of antibodies targeting PD-1 and SIRP reduced senescent cell accumulation and rescued the renal pathology conferred by hematopoietic LOY. These data indicate that hematopoietic LOY contributes to pathologic conditions by impairing the clearance of senescent cells through upregulation of immune checkpoint proteins.
2025-07-09 | GSE301560 | GEO
Project description:The healthspan of mice is enhanced by selectively killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and burden of age-related chronic diseases. As senescent cells resist apoptosis, we used microarrays to identify transcripts and pathways that differ between senescent and non-senescent preadipocytes, and might be involved in resistance to apoptosis. Primary human abdominal subcutaneous preadipocytes were isolated from 8 healthy lean kidney donors. All subjects were matched by age,gender and BMI. The protocol was approved by the Mayo Clinic Foundation Institutional Review Board for Human Research. Preadipocytes were radiated at 10 Gy to induce senescence or were sham-radiated. From senescent cells RNA was isolated 20 days after irradiation.
2015-03-10 | E-GEOD-66236 | biostudies-arrayexpress
Project description:Several reports have focused on the identification of biological elements involved in the development of abnormal systemic biochemical alterations in chronic kidney disease, but this abundant literature results most of the time fragmented. To better define the cellular machinery associated to this condition, we employed an innovative high-throughput approach based on a whole transcriptomic analysis and classical biomolecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both chronic kidney disease patients in conservative treatment (CKD, n=9) and hemodialysis (HD, n=17) compared to healthy subjects (NORM) (p<0.001, FDR=1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system (OXPHOS). Western blotting for COXI and COXIV, key constituents of the complex IV of OXPHOS, performed on an independent testing-group (12 NORM, 10 CKD and 14 HD) confirmed the elevated synthesis of these subunits in CKD/HD patients. However, complex IV activity was significantly reduced in CKD/HD patients compared to NORM (p<0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to NORM. Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress. Experiment Overall Design: For microarray analysis, we studied subjects included in the training group. This population included 8 healthy subjects (NORM), 9 patients with Chronic kidney disease (CKD) on stage II-III (CKD II-III) (mean±SD of estimated GFR by MDRD formula: 41.4±4.3 ml/min) and 17 patients undergoing hemodialysis treatment (HD).All HD patients were stably treated, for at least 1 year, three times a week (4-5 hours per session), using synthetic membrane dialyzers. During the study period, no CKD patients received dialysis treatment. In addition, all patients suffering from infectious diseases, diabetes, chronic lung diseases, neoplasm, or inflammatory diseases and patients receiving antibiotics, corticosteroids, or nonsteroidal anti-inflammatory agents were excluded. No patients had symptomatic coronary artery diseases or a family history of premature cardiovascular diseases. For all subjects, 20 ml of whole blood were collected. For HD patient the biological material was obtained at the beginning of the second HD session of the week. PBMC were isolated by density separation over a Ficoll-PaqueTM (GE healthcare, Sweden) gradient (460g for 30 min). Cells were then counted and their viability was assessed by trypan blue exclusion (>90% PBMC were viable). Total RNA was isolated by RNeasy mini kit Qiagen (QIAGEN AG, Basel, Switzerland) from a minimum of 5 milion cryopreserved PBMC. RNA was, then, processed and hybridized to the GeneChip Human Genome Plus 2.0 or U133A oligonucleotide microarray (Affymetrix, Santa Clara, CA, USA)
2009-12-04 | E-GEOD-15072 | biostudies-arrayexpress
Project description:Single cell analysis of senescent cells of old p16-FDR mice (kidney)
| PRJNA683860 | ENA
Project description:Epidemiological studies indicate that adverse intrauterine and postnatal environment has a long-lasting role in chronic kidney disease (CKD) development. Epigenetic information can represent a plausible carrier for mediating this "programming" effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and CKD tubule samples obtained from patients show significant differences. We rarely observed differentially methylated regions (DMR) on promoters. Histone modification-based kidney specific genome-wide gene regulatory region annotation maps (promoters, enhancers, transcribed and repressed regions) were generated. DMRs mostly overlapped with putative enhancer regions and were enriched in consensus binding sequences for important renal transcription factors, indicating their importance in gene expression regulation. A core set of genes, including transforming growth factors and collagens, showed cytosine methylation changes correlating with downstream transcript levels. Our report raises the possibility that epigenetic dysregulation plays a role in CKD development via influencing core profibrotic pathways. HG18_HELP array We used custom-commercial array to detail the differences of methylation regions of human tubule epithelial cells between chronic kidney disease and normal. We sought to decrease the cell type heterogeneity of kidney tissues to increase the resolution of methylation profiles. To that end, microdissected human kidney tissue from both chronic kidney disease patient and normal are used for the HELP-assay (HpaII tiny fragment Enrichment by Ligation-mediated PCR) and hybridization on Roche NimbleGen microarrays.
2013-08-09 | E-GEOD-49557 | biostudies-arrayexpress
Project description:The study included 75 participants, among whom 51 patients were diagnosed with kidney diseases: Calculus of kidney (N20.0, URCD) and Cyst of kidney (N28.1, ACDK), Malignant neoplasm of kidney, except renal pelvis (С64, RNCL) and 24 conditionally healthy participants (CNTR).
2025-01-07 | PXD051799 | Pride
Project description:Epidemiological studies indicate that adverse intrauterine and postnatal environment has a long-lasting role in chronic kidney disease (CKD) development. Epigenetic information can represent a plausible carrier for mediating this programming effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and CKD tubule samples obtained from patients show significant differences. Cytosine methylation changes showed high concordance (98%) with a large (n=87) replication dataset. We rarely observed differentially methylated regions (DMR) on promoters. Histone modification-based kidney specific genome-wide gene regulatory region annotation maps (promoters, enhancers, transcribed and repressed regions) were generated. DMRs mostly overlapped with putative enhancer regions and were enriched in consensus binding sequences for important renal transcription factors, indicating their importance in gene expression regulation. A core set of genes, including transforming growth factors and collagens, showed cytosine methylation changes correlating with downstream transcript levels. Our report raises the possibility that epigenetic dysregulation plays a role in CKD development via influencing core profibrotic pathways. We used microarrays to detail the differences of gene expression of human tubule epithelial cells between chronic kidney disease and normal. We sought to decrease the cell type heterogeneity of kidney tissues to increase the resolution of expression profiles. To that end, microdissected human kidney tissue from both chronic kidney disease patient and normal are used for RNA extraction and hybridization on Affymetrix microarrays.
2013-07-18 | E-GEOD-48944 | biostudies-arrayexpress
Project description:In Brazil, the incidence and prevalence of CKD are increasing, the prognosis remains poor and the costs of treating the disease are very high. Added to this is the increase in the main risk factors for the development and progression of CKD, such as greater aging of the population, high prevalence of AH, DM, overweight, smoking and others, which suggests the continuation of CKD as a serious problem of public health. This situation requires prevention actions, early diagnosis of the disease and agile action in the face of the functional changes evidenced. Furthermore, there is a need to find ways to prevent the progression of the disease. A disturbing issue in nephrology practice is the observation that a significant number of CKD patients lose renal function asymptomatically. One of the reasons is late diagnosis and referral to dialysis. The main causes are: the fact that CKD is often asymptomatic, difficulty in diagnosis, tendency of doctors not to refer patients adequately, selection of patients with less morbidities to start dialysis, resistance of patients to treatment, deficient structure of the health system and lack of access to treatment. The consequences of late referral are reflected in greater morbidity, mortality, costs and worse quality of life. In this sense, it is important to search for new markers of the disease that allow early diagnosis, monitoring of progression and, eventually, improving response to treatment. Analyzing mechanisms underlying renal failure and identifying unique biomarkers (such as metabolite ratios) have the potential to increase our understanding of CKD and improve disease diagnosis and treatment algorithms. In this sense, this project can represent important progress in CKD proteomics research, based on complex information obtained from proteomics associated with basic medical information. New biomarkers are needed as non-invasive tools to aid the accurate diagnosis of kidney diseases with similar clinical characteristics but different prognosis. This project aims to investigate the proteomics of saliva from chronic kidney disease patients in the search for molecular markers that can be used in both the diagnosis and prognosis of the disease. So, for this, it was necessary to select healthy individuals and chronic kidney disease patients, and collect sociodemographic, behavioral, food consumption, clinical and anthropometric data from these individuals. Next, the mass spectrometry proteomics technique was performed on saliva samples and investigated molecules that could be used as markers of CKD and other associated comorbidities, in addition to evaluating whether any molecule could be indicative of the progression of CKD.
2024-12-17 | PXD045874 | Pride