PXD042533

PXD042533 is an original dataset announced via ProteomeXchange.

Title	Matrix Metalloproteinase-7 in Urinary Extracellular Vesicles Identifies Rapid Disease Progression in Autosomal Dominant Polycystic Kidney Disease
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.
HostingRepository	PRIDE
AnnounceDate	2023-12-18
AnnouncementXML	Submission_2023-12-18_04:28:36.328.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-30 03:44:54	ID requested
⏵ 1	2023-12-18 04:28:36	announced

10.1681/ASN.0000000000000277;

submitter keyword: Autosomal Dominant Polycystic Kidney Disease,Urinary Extracellular Vesicles,Matrix Metalloproteinase-7

Jeroen Demmers
contact affiliation	Erasmus MC
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042533
     1. Label: PRIDE project
     2. Name: Matrix Metalloproteinase-7 in Urinary Extracellular Vesicles Identifies Rapid Disease Progression in Autosomal Dominant Polycystic Kidney Disease