Proteomic profiling of extracellular vesicles (EVs) isolated from peritoneal dialysis effluent (PDE) of short-term (SPD) and long-term (LPD) PD patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Pei Zhang
PROVIDER: PXD078788 | iProX | Sat May 23 00:00:00 BST 2026
REPOSITORIES: iProX
Similar Datasets
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:To define the transcriptomic landscape of human mesothelial cells in response to PD, we analyzed single cell transcriptomes including cells dissociated from normal peritoneum (hernia surgery, n = 3), and peritoneal cells from effluent of short-term PD patients (PD less than 2 weeks, n = 6) and from long-term PD patients (PD more than 6 years, n = 4) ,we demonstrate that mesothelial cells develop hyperglycolysis, a metabolic alteration that is correlated with the development of peritoneal fibrosis.
2019-06-09 | GSE130888 | GEO
Project description:Introduction: Peritoneal fibrosis (PF), a major complication of long-term peritoneal dialysis (PD), is characterized by excessive extracellular matrix (ECM) deposition mediated by activated myofibroblasts (MyoFs). While mesenchymal transition of mesothelial cells has been widely studied, the cellular origins of MyoFs remain incompletely defined. Recent evidence suggests pericytes—mural cells surrounding microvessels—may contribute to fibrosis in other organs, but their role in PF pathogenesis is undefined. Objective: This study aimed to clarify pericyte-myofibroblast transition (PMT) as a novel mechanism in PF, investigate the role of platelet-derived growth factor receptor-β (PDGFRβ) signaling in orchestrating PMT, and evaluate the therapeutic potential of natural triterpenoid asiaticoside (ASI) against PDGFRβ-driven fibrosis. Methods and Results: Through single-cell RNA sequencing of chlorhexidine gluconate (CG)-induced PF mice, we identified two MyoFs subpopulations (Fibro5 and Fibro7) exhibiting pericyte lineage signatures, with trajectory inference confirming their differentiation from pericytes during fibrosis. Pharmacological and genetic approaches demonstrated that PDGFRβ signaling orchestrates PMT, as evidenced by upregulated α-smooth muscle actin (α-SMA), PDGFRβ, and ECM markers (collagen I, fibronectin) in PF mice and TGF-β1/PDGF-BB-stimulated mouse peritoneal microvascular pericytes. Remarkably, ASI attenuated PF by suppressing PDGFRβ expression by 50% and disrupting pericyte-endothelial interactions, which led to a marked reduction in peritoneal thickness (by ~69%) and collagen deposition (by ~78%). Proteomics analysis provided a perspective for analyzing the downstream mechanisms. Mechanistically, ASI mimicked PDGFRβ knockout effects, reducing MyoFs accumulation and abrogating PDGFRβ-induced Erk and Pi3k/Akt activation. Conclusion: Our findings repositioned pericytes as pivotal contributors to PF and proposed ASI as a therapeutic agent against PDGFRβ-driven PMT, which provided a new perspective for antifibrotic strategies.
2025-10-30 | PXD070069 |
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:Peritoneal dialysis (PD) is a widely used kidney replacement therapy for patients with end-stage kidney disease. Nevertheless, long-term exposure to PD fluid can damage the peritoneal membrane, leading to ultrafiltration failure and, ultimately, discontinuation of PD. Investigation of the molecular mechanisms underlying this damage is essential for identifying new therapeutic targets to mitigate peritoneal deterioration in PD patients. To this end, we employed RNA sequencing in a preclinical model of peritoneal injury, induced by prolonged chlorhexidine (CHX) exposure, which revealed cytosolic DNA-sensing signaling as a novel pathway. Next, we demonstrated that key players in this pathway, such as the stimulator of interferon genes (STING) and its downstream signaling effectors (interferon regulatory factor 3, interferon-stimulated genes, and nuclear factor-κB signaling), were upregulated in experimental peritoneal damage. Moreover, increased STING expression was observed in human peritoneal biopsies from patients with PD. Subsequent studies in STING-deficient mice showed reduced proinflammatory gene expression and immune cell infiltration, together with inhibited nuclear factor-κB pathway activation at both early (10 days) and late (30 days) stages of CHX-induced peritoneal injury. STING deficiency also reduced peritoneal membrane thickening, fibrosis, and mesothelial-to-mesenchymal transition (MMT)-related changes in advanced CHX-induced damage. Furthermore, pharmacological inhibition of STING with C-176 attenuated CHX-induced peritoneal inflammation. Macrophages were identified as one of the STING-expressing cell types in the injured peritoneum. Hence, in vitro STING blockade in activated macrophages inhibited MMT in cultured mesothelial cells, suggesting that STING activation in this population may drive peritoneal fibrosis. Additionally, STING deficiency reduced peritoneal inflammation in S. epidermidis-induced peritonitis and decreased adhesion scores in a postsurgical intra-abdominal adhesion model. These findings identify STING as a pivotal mediator of peritoneal injury and support its potential as a novel therapeutic target to prevent PD-associated ultrafiltration failure. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
2024-11-25 | GSE282440 | GEO
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:Peritoneal dialysis related fibrosis (PD-related fibrosis) is one of the most common complications of PD and one of the main reasons for patients to stop PD, occurring almost exclusively in all long-term PD patients. The mechanism of PD-related fibrosis is currently not fully understood. Previous studies have shown that it is related to frequent peritonitis and the epithelial-mesenchymal transition (more accurately, mesothelial-mesenchymal transition) of peritoneal mesothelial cells caused by high glucose and high osmotic non physiologically compatible PD fluid. Due to the lack of effective prevention and treatment methods for PD-related fibrosis, the study of its mechanism is of great clinical significance. Collecting dialysis fluid from patients after 3 years of PDfor single-cell sequencing can help observe changes in the peritoneal environment and structural composition during dialysis, providing a new perspective for the prevention and treatment of PD-related fibrosis.
2025-12-10 | GSE297829 | GEO
Project description:Fushen Granule (FSG), a Chinese medicinal formular, was clinically used to improve the peritoneal dialysis (PD) efficiency in ESRD patients received PD treatment. However, its mechanisms of anti-fibrotic effect in peritoneal fibrosis (PF) has not been studied yet. In this work, we used TGF-β1-stimulated MeT5A cells to mimic the process of PF in vitro, and Label-free proteomics and bioinformatics analysis were used to explored the underlying targets and pathways of FSG on TGF-β1-treated MeT5A cells
2022-04-20 | PXD033058 | Pride
Project description:To characterize the metabolic profile of peritoneal endothelial cells (ECs) in response to peritoneal dialysis (PD), we performed RNA sequencing of peritoneal ECs isolated from mice treated with PD fluid for 6 weeks (n = 3) and from mice treated with saline for 6 weeks (n = 3). We demonstrated that peritoneal ECs had a hyperglycolytic metabolism in response to PD fluid treatment, which is associated with the development of microvascular alterations and peritoneal dysfunction.
2023-12-06 | GSE230008 | GEO