MiRNA sequencing revealed differentially expressed exosomes miRNAs in PDE of patients with peritoneal ultrafiltration failure
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182736 | GEO | 2021/08/27
REPOSITORIES: GEO
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Project description:MiRNA sequencing revealed differentially expressed exosomes miRNAs in PDE of patients with peritoneal ultrafiltration failure
| PRJNA757643 | ENA
Project description:Chronic exposure to biological incompatibility of peritoneal dialysis solution is one of the principal causes of ultrafiltration failure (UF). However, the changes of peritoneal cell composition and molecular mechanism of peritoneal microenvironment after long-term PD are unclear. Single-cell RNA sequencing was performed to profile cell composition and transcriptome characteristics in effluent obtained from patients undergoing PD with short vintage (SV), long vintage without ultrafiltration failure (LV_NOT_UF), and long vintage with ultrafiltration failure (LV_UF). A total of 6 SV patients, 6 LV_NOT_UF patients, and 4 LV_UF patients were enrolled. The median PD duration of the three groups were 5 months (range:1.0–6.0 months), 137 months (range: 92–189 months) and 132 months (range: 120–161 months), with no significant differences in age (38.3 ± 21.5 years, 45.7 ± 10.6 years and 41.0 ± 16.7 years, P>0.05) and gender (male%: 33.3%, 50.0% and 25.0%, P>0.05). scRNA-seq data annotated 8 main cell types including epithelial-like mesothelial cells (E-MCs), mesenchymal-like mesothelial cells (M-MCs), fibroblast, plasma B cells, conventional dendritic cells, plasmacytoid dendritic cells, natural killer T cells, and myeloid cells. LV_UF patients showed higher proportion of E-MCs, which exhibited activated autophagy and had properties of both anti-inflammatory and pro-inflammatory, and neutrophil- and autophagy-related DEGs of E-MCs were upregulated in the LV_UF group. In contrast, the M-MCs and the AQP1 expression in the peritoneal mesenchyme were reduced in the LV_UF group compared to the other groups. The neutrophils in PD effluent were elevated in the LV_UF group, while the M2-like MRC1-macrophages gradually decreased from the SV, LV_NOT_UF to LV_UF group. Compared with the LV_NOT_UF group, the upregulated DEGs of monocytes/macrophages in the LV_UF group not only involved in pro-inflammatory response, but also promoted EMT progress. Additionally, neutrophils and monocytes/macrophages both interacted with MCs. Our study uncovers peritoneal different individual cell populations and cellular functions in different stages of PD which indicates the dynamic changes of microenvironments of peritoneal membrane. These findings provide new insights into the novel roles of mesothelial cells and inflammatory cells in UF.
2023-11-27 | GSE248762 | GEO
Project description:Peritoneal fibrosis is a major complication of long-term peritoneal dialysis (PD), leading to ultrafiltration failure and sometimes life threatening encapsulating peritoneal sclerosis. Fibrosis is driven by activated myofibroblasts that are derived, in part, from mesothelial-to-mesenchymal transition (MMT). We aimed to discover novel mediators of MMT and then experimentally exploit them to prevent peritoneal fibrosis. Using an antibody to HBME-1 and streptavidin nanobead technology, we first pioneered a novel method to purify rat mesothelial cells. After exposing mesothelial cells to transforming growth factor β1 (TGFβ1), we undertook RNAseq whole transcriptome analyses and outlined, the expression profile of sorted mesothelial cells at pre- and post- MMT.
2018-06-18 | E-MTAB-5998 | biostudies-arrayexpress
Project description:Proteomics-based analysis of Peritoneal Dialysis Effluent is a relatively new approach to studying the changes associated with PD. Recent studies have shown altered proteomic profiles in various conditions of PD patients, including uremia, diabetes, peritonitis, abnormal peritoneal transport function and with different peritoneal dialysis modality. However, these studies extracted proteins in PDE by precipitation techniques resulting in high abundant diffusible proteins from blood circulation which interfered with the identification of low abundant, locally secreted, yet important, biomarkers. we hypothesize that EVs are secreted from peritoneal resident cells and contain known biomarkers for PDE-related membrane injury. As a proof of concept, here we identified and characterized EVs from PDE of healthy PD patients using transmission electron microscopy (TEM), dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA). Furthermore, we did proteomics and bioinformatics analyses to determine the number and type of proteins measurable within EVs isolated from the PDE using two methods of vesicle isolation.
2018-08-14 | PXD006371 | Pride
Project description:Peritoneal dialysis (PD) is a successful renal replacement therapy for end-stage renal disease that effectively improves the quality of life. Long-term PD causes epithelial mesenchymal transformation (MMT) of peritoneal mesothelial cells, leading to peritoneal fibrosis which reduces the efficiency of PD. Macrophages are considered players in the onset and perpetuation of peritoneal injury. Yet, the mechanisms employed by macrophage-mesothelial cells communication to regulate peritoneal fibrosis are not fully elucidated resulting in lack of disease-modified drugs. This study analyzes the role of macrophage-mesothelial cell communication by intraperitoneal injection of macrophage derived exosomes in PD model rats. These results show that macrophages secrete exosomal miR-204-5p that directly targets Foxc1, leading to the activation of MMT in mesothelial cells. The data also shows that intraperitoneal injection of dissolved AS-IV can improve MMT by altering macrophage derived exosomal miRNAs. This study indicates that intercellular crosstalk between peritoneal macrophages and mesothelial cells is mediated by macrophage derived miR-204-5p-containing exosomes that control the MMT progression, providing AS-IV for prevention and treatment of PD induced peritoneal fibrosis. Our results demonstrate, for the first time, a novel role of the AS-IV on miR-204-5p/Foxc1/β-catenin axis in improving peritoneal fibrosis in vivo and vitro.
2023-01-01 | GSE165342 | GEO
Project description:Peritoneal dialysis (PD) is a widely used kidney replacement therapy for end-stage renal failure patients. However, long-term exposure to PD fluids (PDF) can lead to peritoneal membrane (PM) damage, causing ultrafiltration failure and thus PD. Investigating the molecular mechanisms underlying this damage is crucial for identifying new therapeutic targets to mitigate peritoneal deterioration in PD patients. In this work we study the role of the stimulator of interferon genes (STING), a key factor in recognising cytoplasmic DNA, in peritoneal inflammation and fibrosis. To this aim, we performed different preclinical mouse models of peritoneal inflammation, fibrosis, and adhesions. In a model of chlorhexidine gluconate (CHX)-induced inflammation significant changes in the peritoneal transcriptomic profile indicated that cytosolic DNA signaling was one of the most enriched KEGG pathways. In agreement with this finding, STING was upregulated in CHX- and PDF-exposed mice, and in peritoneal biopsies from PD patients. In early and advanced stages of the CHX models, STING genetic deficiency diminished peritoneal inflammation by preventing NF-κB pathway activation, downregulating inflammatory gene expression, and decreasing immune cell infiltration. STING absence also decreased PM thickness and fibrosis in the advanced CHX model, reduced adhesion scores in a post-surgical intra-abdominal adhesion model, and decreased inflammation in a S. epidermidis-induced peritonitis model. Furthermore, pharmacological inhibition of STING with C-176 decreased inflammation and macrophage-mediated mesothelial-to-mesenchymal transition in cultured mesothelial cells, and reduced CHX-induced PM thickness and inflammation in mice. Altogether, these findings highlight STING as a key mediator of peritoneal damage and suggest it may be a novel therapeutic target for preventing PD-associated peritoneal deterioration.
2024-11-25 | GSE282440 | GEO
Project description:Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the high volumes of available PD effluent (PDE) represents a rich source of biomarkers for monitoring disease and therapy. Although this information could help guiding the management of PD patients, little is known about the potential of PDE to define pathomechanism-associated molecular signatures in PD. Here we present the utilization of a high-performance multiplex proteomics approach based on depletion of highly abundant plasma proteins and enrichment of low abundance proteins and quantitation using a combination of label-free and isobaric labeling strategies for PDE samples from PD patients (n=20), who received either standard PD fluid or a novel PD fluid (added alanyl-glutamine (AlaGln)) in an open-label, randomized, two-period, cross-over clinical trial.
2012-12-13 | PXD006863 | Pride
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
Project description:Single-cell transcriptomics uncovers the roles of mesothelial cells and microenvironmental changes in the ultrafiltration failure after long-term peritoneal dialysis
| PRJNA1045728 | ENA
Project description:Peritoneal macrophages from healthy New Zealand White rabbits were treated with exosomes from Cysticercus pisiforms and treated with PBS were used as control.
2022-04-21 | PXD033317 |