PXD012210

PXD012210 is an original dataset announced via ProteomeXchange.

Title	Urinary peptidomics in youths with and without type 1 diabetes
Description	Although the early mechanisms responsible for diabetic kidney disease remain unclear, it is widely believed that chronic hyperglycemia disrupts the proteolytic milieu in the diabetic kidney and may contribute to early kidney injury. We thus performed mechanistic peptidomics in type 1 diabetes before the onset of microalbuminuria. In the discovery cohort of 30 participants, we identified 6550 peptides from 753 proteins. After removing false hits and potential contaminants, there were 6323 quantified peptides: 5708 peptides can be found in youths with type 1 diabetes, 5011 in healthy controls, and 4396 common to both groups. After applying a cut-off of 100%, there were 162 peptides found in each and every urine sample. From this subset, fifteen peptides were differentially excreted between youths with type 1 diabetes and their non-diabetic peers (P < 0.05, t-test); five remained significant after Benjamini-Hochberg adjustment (Q < 0.05). Excretion rates of six peptides were validated in a second cohort of thirty participants using parallel reaction monitoring (separate PRIDE file). Interestingly, these peptides originated from a small region near the C-terminus of uromodulin, a kidney-specific protein. In silico analyses of cleavage sites implicated several metallo and serine proteases involved in wound healing. Two of the uromodulin peptides activated NFκB in a TLR4-dependent manner in cultured kidney tubular cells and also promoted neutrophil migration in vitro. In summary, the differential excretion of uromodulin peptides may shed light onto early inflammatory processes in the diabetic kidney.
HostingRepository	PRIDE
AnnounceDate	2020-01-20
AnnouncementXML	Submission_2020-01-20_01:19:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julie Anh Dung Van
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-02 00:48:45	ID requested
⏵ 1	2020-01-20 01:19:27	announced

Van JAD, Clotet-Freixas S, Zhou J, Batruch I, Sun C, Glogauer M, Rampoldi L, Elia Y, Mahmud FH, Sochett E, Diamandis EP, Scholey JW, Konvalinka A, . Mol Cell Proteomics, 19(3):501-517(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, urine, LC-MS/MS, type 1 diabetes, peptidomics

Ana Konvalinka
contact affiliation	Toronto General Hospital, University of Toronto, Toronto, Canada
contact email	ana.konvalinka@mail.utoronto.ca
lab head
Julie Anh Dung Van
contact affiliation	University of Toronto
contact email	julie.van@mail.utoronto.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012210
     1. Label: PRIDE project
     2. Name: Urinary peptidomics in youths with and without type 1 diabetes