PXD050720

PXD050720 is an original dataset announced via ProteomeXchange.

Title	Proteomic Analysis of Urinary Extracellular Vesicles from Patients with ADTKD-HNF1β identifies roles for cilia-related proteins and Serpins
Description	Autosomal dominant tubulointerstitial kidney disease-subtype hepatocyte nuclear factor 1β (ADTKD-HNF1β) is caused by pathogenic variants in or deletions of the gene encoding transcription factor HNF1β. Patients with the same mutation have variable renal and extrarenal phenotypes, including renal cysts, diabetes, and electrolyte disturbances. The aim of this exploratory study was to provide insight whether pathophysiological effects in the kidney of ADTKD-HNF1β patients are visible by analysing their urinary extracellular vesicle (uEV) proteome. We isolated uEVs collected from patients with ADTKD-HNF1β and included patients with ADPKD and patients with CKD as controls. Subsequently, LC-MS/MS proteomics, and differential and pathway enrichment analyses were performed. Transcriptional targets of HNF1β were selected with ChIP-sequencing to study changes in protein abundance due to loss of HNF1β, and correlation analyses with clinical features were performed. We found differential enrichment of ciliary proteins IFT57, IFT74, IFT81 and IFT88 (adjusted p-value < 0.1), significant enrichment of pathways involved in cell-cell adhesion, and the depletion of several Serpins in patients with ADTKD-HNF1β and APDKD, compared to patients with CKD. We identified differential enrichment of nine HNF1β transcriptional targets between patients with ADTKD-HNF1β and patients with CKD, and we demonstrated that Serpin abundance negatively correlated with eGFR in patients with ADTKD-HNF1β (R = -0.52). The uEV proteome of patients with ADTKD-HNF1β shows a significant enrichment in proteins involved in renal cysts development, with resemblance to ADPKD. These changes provide new insight in the pathophysiology of ADTKD-HNF1β. Their onset and association with cyst development and kidney function decline warrants further study.
HostingRepository	PRIDE
AnnounceDate	2025-03-06
AnnouncementXML	Submission_2025-03-05_23:49:36.851.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pascal Jansen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-18 05:25:56	ID requested
⏵ 1	2025-03-05 23:49:37	announced

Dataset with its publication pending

submitter keyword: Urine, cilia, Serpins, CKD, extracellular vesicles, ADPKD, ADTKD-HNF1B

Jeroen de Baaij
contact affiliation	Department of Medical BioSciences, Radboud Institute for Molecular Life Sciences, Radboud university medical centre, 6500 HB, Nijmegen, The Netherlands.
contact email	Jeroen.debaaij@radboudumc.nl
lab head
Pascal Jansen
contact affiliation	Radboud University
contact email	p.jansen@science.ru.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/03/PXD050720

PRIDE project URI

• PRIDE
  1. PXD050720
     1. Label: PRIDE project
     2. Name: Proteomic Analysis of Urinary Extracellular Vesicles from Patients with ADTKD-HNF1β identifies roles for cilia-related proteins and Serpins