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PXD012389

PXD012389 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUrinary PRM analysis of early type 1 diabetes
DescriptionChronic hyperglycemia is known to disrupt the proteolytic milieu, initiating compensatory and maladaptive pathways in the diabetic kidney. Such changes in intrarenal proteolysis can be captured in the urinary peptidome. We thus examined the urinary peptidomes of otherwise healthy youths with type 1 diabetes and their non-diabetic peers. This cross-sectional study included two separate cohorts for the discovery (N = 30) and initial validation (N = 30) of differential peptide excretion. Peptide bioactivity was predicted using PeptideRanker and subsequently verified in vitro. Proteasix and the Nephroseq database were used to identify putative proteases responsible for peptide generation and examine their expression in diabetic nephropathy. A total of 6550 urinary peptides were identified in the discovery analysis. Of the 15 differentially excreted peptides (P < 0.05), seven derived from a small region (589SGSVIDQSRVLNLGPITRK607) near the C-terminus of uromodulin. Excretion rates of five uromodulin peptides were validated using parallel reaction monitoring (P < 0.05). One of the validated peptides activated TLR4-dependent NFκB signalling, stimulated cytokine release, and enhanced neutrophil migration in vitro. In silico analyses identified several possible proteases such hepsin, cathepsin B, and meprin A to be responsible for generating these peptides. In summary, uromodulin processing in the kidney produces bioactive peptides, which may be differentially excreted in early diabetes.
HostingRepositoryPanoramaPublic
AnnounceDate2020-01-01
AnnouncementXMLSubmission_2020-01-01_17:28:54.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJulie Van
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Oxidation; Label:13C(6)15N(2); Label:13C(6)15N(4)
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-01-16 13:51:50ID requested
12020-01-01 17:28:55announced
Publication List
Van JAD, Clotet-Freixas S, Zhou J, Batruch I, Sun C, Glogauer M, Rampoldi L, Elia Y, Mahmud F, Sochett E, Diamandis EP, Scholey J, Konvalinka A, . Mol Cell Proteomics, ():(2019) [pubmed]
Keyword List
submitter keyword: urine, peptidomics, type 1 diabetes, kidney disease
Contact List
Ana Konvalinka
contact affiliationUniversity Health Network, Toronto, Ontario, Canada
contact emailana.konvalinka@uhn.ca
lab head
Julie Van
contact affiliationUniversity of Toronto
contact emailjulie.van@mail.utoronto.ca
dataset submitter
Full Dataset Link List
Panorama Public dataset URI