Peritoneal Dialysis Induces Alterations In The Transcriptome Of Peritoneal Cells Before Detectible Peritoneal Functional Changes
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ABSTRACT:
PROVIDER: PRJNA516633 | ENA |
REPOSITORIES: ENA
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Project description:Long-term peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. Inflammation may be the key moment and consequently fibrosis, the end result of chronic inflammatory reaction. The objective of the study was to identify genes involved in peritoneal alterations during PD by comparing transcriptome of peritoneal cells in short- and long-term PD patients. Peritoneal effluent of the long-dwell of stable PD patients was centrifuged to obtain peritoneal cells. Gene expression profiling of peritoneal cells using microarray between short- and long-term PD patients was compared. Based on microarray analysis 31 genes for RT-qPCR validation were chosen. A 4-hour peritoneal equilibration test (PET) was performed on the day after the long dwell. Transport parameters and proteins appearance rates were assessed. Genes involved in the immune system process, immune response, cell activation, leuko- and lymphocyte activation were found to be substantially up-regulated in the long-term group. RT-qPCR validation showed higher expression of CD24 (CD24 molecule), LY9 (lymphocyte antigen 9 ), TNFRSF4 (tumor necrosis factor receptor superfamily, member 4), CD79A (CD79a molecule, immunoglobulin-associated alpha), CCR7 (chemokine (C-C motif) receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor, alpha) in long-term PD patients, CD24 having the best discrimination ability between short- and long-term treatment. A relationship between CD24 expression and genes for collagen and matrix formation was shown. Activation of CD24 provoked by pseudohypoxia due to extremely high glucose concentrations in dialysis solutions might play the key role in the development of peritoneal membrane alterations.
2019-01-24 | GSE125498 | GEO
Project description:Transcriptome analysis of two population of peritoneal mononuclear phagocytes (CD14+ macrophages and CD1c+ dendritic cells) in peritoneal dialysis effluent from stable (infection-free) peritoneal dialysis patients.
2017-01-23 | E-MTAB-5439 | biostudies-arrayexpress
Project description:The complete systemic deregulated biological network in peritoneal dialysis (PD) patients is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition. For the transcriptomic part of the study, we analyzed new data from 10 patients undergoing peritoneal dialysis .
2023-12-31 | E-MTAB-12875 | biostudies-arrayexpress
Project description:Biological Determinants of Peritoneal Dialysis Outcomes
| PRJNA860263 | ENA
Project description:Biological Determinants of Peritoneal Dialysis Outcomes
| PRJNA860262 | ENA
Project description:Expression data from peritoneal biopsies of patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first implantation of a peritoneal dialysis catheter (PD), and patients undergoing abdominal surgery for non-peritoneal conditions (controls) We used microarrays to determine the transcriptional profiles of peritoneal membrane in patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first insertion of a peritoneal dialysis cathetier (PD), and uremic patients without history of PD or EPS, undergoing abdominal surgery for non-peritoneal problems (CON) Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality. EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups. Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value <0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples. The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment.
2014-11-04 | GSE62928 | GEO
Project description:Peritoneal fibrosis is regard as a significant cause of the loss of peritoneal function, markedly limiting the application of peritoneal dialysis(PD). However, the pathogenesis of peritoneal fibrosis remains unclear. Tissue-derived extracellular vesicles(EVs) mediate intercellular communications and play a central role in organ fibrosis. We performed a proteomics profiling of EVs from normal peritoneum and PD-induced fibrotic peritoneum in mice.
2023-01-25 | PXD037945 | Pride
Project description:Expression data from peritoneal biopsies of patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first implantation of a peritoneal dialysis catheter (PD), and patients undergoing abdominal surgery for non-peritoneal conditions (controls) We used microarrays to determine the transcriptional profiles of peritoneal membrane in patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first insertion of a peritoneal dialysis cathetier (PD), and uremic patients without history of PD or EPS, undergoing abdominal surgery for non-peritoneal problems (CON) Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality. EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups. Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value <0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples. The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment. Total RNA was isolated from frozen peritoneal biopsy specimens obtained at time of surgery. RNA was hybridized to Affymetrix arrays, and analyzed. Select transcripts were subjected to validation by rt-pcr and by immunodetection.
2014-11-04 | E-GEOD-62928 | biostudies-arrayexpress
Project description:In this open-label randomized controlled phase I/II trial, 20 stable peritoneal dialysis patients underwent two 4 h dwells with acidic glucose-based PDF, with and without 8 mM alanyl-glutamine (AlaGln) in a cross-over design. Unsupervised hierarchical clustering of transcriptomics data suggested specific effects of AlaGln in patients who had previously suffered from peritonitis.
2020-01-24 | GSE57070 | GEO
Project description:Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by corticoresistant primary focal segmental glomerulosclerosis), a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed a complete distinction of the whole proteomic exosome mesothelial content of FSGS versus No FSGS (with 100% accuracy). Out of the 2490 identified proteins, 40% (995) were involved in epithelial-mesenchymal transition (EMT)/fibrosis and in the transforming growth factor-β pathway. Additionally, the Weight Gene Co-expression Network Analysis algorithm identified that some of the discriminative proteins (TIMP1, CTHRC1, SPARC, CHMP4B, COL5A2, ANXA13, FNC2 and CENP-E) were also highly correlated to PD vintage, fibrosis, EMT and non-neoplastic PM disease. All together our data demonstrated that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery with exosomes having a primary role in this process. Moreover, they indicated that identified FSGS-associated elements in mesothelial exosome protein could be employed as potential new biomarkers of mesothelial integrity. Finally, our results highlighted that in FSGS patients particular attention should be paid to use more biocompatible dialysis solution, reduce the length of time on PD and personalize PD regimens to minimize the risk of rapid loss of PM function or development of encapsulating peritoneal sclerosis.
2022-02-17 | PXD024556 | Pride