Dataset Information

Proteomic landscape of plasma and plasma-derived sEVs and lEVs in uveitis and posterior scleritis

ABSTRACT: Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis, accurate diagnosis remains challenging. Here, two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, were obtained from patients with uveitis and posterior scleritis and subjected to proteomics analysis alongside plasma. We identify 3,658 proteins, with 3,097, 3,312, and 2,820 quantifiable proteins for sEVs, lEVs, and plasma, respectively. The proteomes of the two EV subgroups differed significantly and were more highly correlated with disease development than that of plasma. Comprehensive bioinformatics analysis of the EVs and plasma highlighted a potential pathogenic mechanism for these diseases. Four potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 levels and mean retinal thickness. This study provides a proteomic landscape of the molecular changes in plasma and EVs involved in four diseases, offers insights into their potential pathogenesis, and identifies valuable biomarker candidates.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xiaomin Zhang

PROVIDER: PXD036844 | iProX | Mon Sep 19 00:00:00 BST 2022

REPOSITORIES: iProX

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Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration.

Wu Lingzi L Zhou Lei L An Jinying J Shao Xianfeng X Zhang Hui H Wang Chunxi C Zhao Guixia G Chen Shuang S Cui Xuexue X Zhang Xinyi X Yang Fuhua F Li Xiaorong X Zhang Xiaomin X

Journal of translational medicine 20230615 1

<h4>Background</h4>Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging.<h4>Methods</h4>Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformati ...[more]

PMID: 37322475

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.

Dataset Information

Proteomic landscape of plasma and plasma-derived sEVs and lEVs in uveitis and posterior scleritis

Publications

Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration.

Similar Datasets

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