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PXD025547-2

PXD025547 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic Analysis of Urinary Extracellular Vesicles Reveals a Role for the Complement System in Medullary Sponge Kidney Disease
DescriptionMedullary sponge kidney (MSK) disease is a rare and neglected kidney condition often associated with nephrocalcinosis/nephrolithiasis and cystic anomalies in the precalyceal ducts. Little is known about the pathogenesis of this disease, so we addressed the knowledge gap using a proteomics approach. The protein content of microvesicles/ exosomes isolated from urine of 15 MSK and 15 idiopathic calcium nephrolithiasis (ICN) patients was investigated by mass spectrometry, followed by weighted gene coexpression network analysis, support vector machine (SVM) learning, and partial least squares discriminant analysis (PLS-DA) to select the most discriminative proteins. Proteomic data were verified by ELISA. We identified 2998 proteins in total, 1764 (58.9%) of which were present in both vesicle types in both diseases. Among the MSK samples, only 65 (2.2%) and 137 (4.6%) proteins were exclusively found in the microvesicles and exosomes, respectively. Similarly, among the ICN samples, only 75 (2.5%) and 94 (3.1%) proteins were exclusively found in the microvesicles and exosomes, respectively. SVM learning and PLS- DA revealed a core panel of 20 proteins that distinguished extracellular vesicles representing each clinical condition with an accuracy of 100%. Among them, three exosome proteins involved in the lectin complement pathway maximized the discrimination between MSK and ICN: Ficolin 1, Mannan-binding lectin serine protease 2 and Complement component 4-binding protein β. ELISA confirmed proteomic results. Our data show that the complement pathway is involved in MSK, revealing a new range of potential therapeutic targets and early diagnostic biomarkers.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:52:06.825.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMartina Bartolucci
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion ETD
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-22 00:23:23ID requested
12022-01-14 07:51:18announced
22023-11-14 08:52:07announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: medullary sponge kidney
idiopathic calcium nephrolithiasis
complement system
proteomics
Contact List
Andrea Petretto
contact affiliationIRCCS Ist G. Gaslini
contact emaila.petretto@gmail.com
lab head
Martina Bartolucci
contact affiliationIRCCS Gaslini
contact emailsmartibartolucci@gmail.com
dataset submitter
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Dataset FTP location
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