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Quantitative proteome of urinary extracellular vesicles (uEVs) from hypertensive patients with raised aldosterone-to-renin ratios (ARRs) that underwent seated saline suppression testing (SSST)

ABSTRACT: This dataset contains quantitative proteome from Tandem Mass Tag (TMT) based quantitative proteomic analysis on uEVs from hypertensive patients with raised aldosterone-to-renin ratios (ARR) that underwent seated saline suppression testing (SSST).

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

SUBMITTER: Qi Wu

LAB HEAD: Robert A. Fenton

PROVIDER: PXD022653 | Pride | 2022-10-13

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	SST-Exosomes-S1-1.raw	Raw
	SST-Exosomes-S1-1_20190821121519.raw	Raw
	SST-Exosomes-S1-2.raw	Raw
	SST-Exosomes-S1-2_20190821140333.raw	Raw
	SST-Exosomes-S1-3.raw	Raw

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Publications

Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles.

Wu Aihua A Wolley Martin J MJ Wu Qi Q Cowley Diane D Palmfeldt Johan J Welling Paul A PA Fenton Robert A RA Stowasser Michael M

Kidney360 20220301 5

<h4>Background</h4>Sodium chloride (NaCl) loading and volume expansion suppress the renin-angiotensin-aldosterone system to reduce renal tubular reabsorption of NaCl and water, but effects on the sodium-chloride cotransporter (NCC) and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated.<h4>Methods</h4>We used urinary extracellular vesicles (uEVs) as an indirect readout to assess renal transmembrane proteins involved in NaCl and wat ...[more]

PMID: 36128481

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Quantitative proteomic analysis of urinary exosomes from patients with primary aldosteronism that underwent fludrocortisone suppression test

Project description:The sodium chloride cotransporters (NCC) and the epithelial sodium channel (ENaC) have been reported to be the main effectors of aldosterone in Na+ and Cl- reabsorption in the distal nephron and dietary K+ downregulates NCC. The Cl-/HCO3- exchanger pendrin has been revealed as a key role in maintaining extracellular fluid and electrolyte homeostasis by regulating Cl- reabsorption in the aldosterone-sensitive distal nephron working in tandem with ENaC and perhaps NCC. Pendrin-mediated Cl-/HCO3- exchange is stimulated in models of metabolic alkalosis (e.g. aldosterone administration or dietary NaHCO3 intake), and plasma K+ level is thought to negatively influence pendrin. In this study we used high-throughput proteomics and bioinformatics approaches to analyze urinary exosome contents isolated from patients undergoing fludrocortisone suppression test (FST, as a means of confirming or excluding primary aldosteronism [PA]) to examine the actions of administration of aldosterone analogs, NaCl and KCl orally on transmembrane proteins existing in urinary exosomes.

2020-11-20 | PXD017083 | Pride

Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer

Project description:One of the challenges of current research in prostate cancer is to improve the differential non-invasive diagnosis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer patients exhibit genuine and differential physical and biological properties. Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in prostate cancer. RNA extraction was performed in 10 ultracentrifuge-isolated-uEVs samples (4 BPH, 6 Pca)

2016-01-13 | E-GEOD-75441 | biostudies-arrayexpress

Protein Profile Changes in the Frontotemporal Lobes in Human Severe Traumatic Brain Injury

Project description:Severe traumatic brain injury (sTBI) is a serious public health issue with high morbidity and mortality rates. Previous proteomic studies on sTBI have mainly focused on human cerebrospinal fluid and serum, as well as on brain protein changes in murine models. However, human proteomic data in sTBI brain is still needed. We used proteomics and bioinformatics strategies to investigate variations in protein expression in human brains after sTBI, using samples from the Department of Neurosurgery, Affiliated Hospital of Hebei University (Hebei, P.R. China). Our proteomics data identified 4031 proteins, of which 162 proteins were overexpressed and 5 proteins were downregulated. The biological pathways that showed significant changes in protein expression according to bioinformatics analysis were glial cell differentiation, complement activation, apolipoprotein catalysis in statin pathway, and the blood coagulation cascade. Western blot verification of protein changes in a subset of the available tissue samples showed results that were consistent with the proteomics data. This study is one of the first to investigate the whole proteome of human sTBI brains, and provides a characteristic signature and overall landscape of the sTBI brain proteome.

2016-04-15 | PXD002783 | Pride

Proteomic Analysis of Urinary Extracellular Vesicles

Project description:Novel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs using a labeled approach (healthy vs. ADPKD) and then using a label-free approach in different subjects (healthy vs. ADPKD vs. non-ADPKD chronic kidney disease [CKD]). In both experiments, thirty proteins were consistently more abundant (≥ 2-fold) in ADPKD-uEVs compared with healthy and CKD uEVs. Of these proteins, periplakin, envoplakin, villin-1, complement C3 and C9 were selected for confirmation, because (1) they were also significantly overrepresented in pathway analysis, and (2) they have been previously implicated in the pathogenesis of ADPKD. Immunoblotting was used to validate the proteomics results, confirming higher abundances of the selected proteins in ADPKD-uEVs in three independent groups of ADPKD-patients. While villin-1, periplakin and envoplakin were more abundant in advanced stages of the disease, complement was already higher in uEVs of young ADPKD patients with preserved renal function. Furthermore, all five proteins correlated positively with height adjusted total kidney volume. The proteins of interest were also analyzed in kidney tissues from kidney-specific-tamoxifen-inducible Pkd1-deletion mice, demonstrating higher expression in more severe stages of the disease. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.

2016-03-15 | PXD003298 | Pride

Expression Analysis of Trimethyltin Chlorides (TMT) Impact on Embryonic Development

Project description:Investigation of whole genome expression pattern of 60 and 72 hours post fertilization Danio Rerio embryos exposed to TMT and vehicle control Embryos were exposed to 10uM TMT or control from 48hpf to 60 or 72 hpf. Three replicates were collected for each time point. 40 embryos were pooled to comprise a replicate.

2011-03-23 | E-GEOD-28131 | biostudies-arrayexpress

Matrix Metalloproteinase-7 in Urinary Extracellular Vesicles Identifies Rapid Disease Progression in Autosomal Dominant Polycystic Kidney Disease

Project description:Background: In autosomal dominant polycystic kidney disease (ADPKD) there is an unmet need for early markers of rapid disease progression to facilitate counseling and selection for kidney-protective therapy. Our aim was to identify markers for rapid disease progression in urinary extracellular vesicles (uEVs). Methods: uEVs were isolated at baseline in two independent cohorts including patients with rapid disease progression and stable disease; patients were matched by age, sex, total kidney volume and mutation. uEV biomarker candidates were identified by mass spectrometry and further analyzed in a third and fourth cohort using immunoblotting and an enzyme-linked immunosorbent assay (ELISA). Single-nucleotide RNA sequencing of healthy and ADPKD tissue was used to confirm findings and identify the cellular origin of the uEV biomarker. Results: In the first two cohorts matrix metalloproteinase-7 (MMP-7) was significantly higher in uEVs of patients with rapid disease progression compared to stable disease. In the third cohort, immunoblotting confirmed a >2-fold increase in uEV-MMP-7 in patients with rapid disease progression compared to stable disease. In the fourth cohort, whole urine rather than uEVs were analyzed with MMP-7 ELISA demonstrating a significant but weak correlation with kidney function decline. Single-nucleotide RNA sequencing showed higher MMP-7 expression in ADPKD kidney tissue than in healthy kidney tissue and localized MMP-7 to the proximal tubule and thick ascending limb. Conclusion: uEV-associated MMP-7 is elevated in ADPKD patients with rapid disease progression and should be further investigated as predictive biomarker. Our findings also suggests that MMP-7 performs better when analyzed in uEVs than in whole urine.

2023-12-18 | PXD042533 | Pride

Endothelial DNA methalytion signature in pulmonary arterial hypertension

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2016-07-15 | E-GEOD-84395 | biostudies-arrayexpress

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