PXD056281

PXD056281 is an original dataset announced via ProteomeXchange.

Title	A patient-derived 3D cyst model of polycystic kidney disease that mimics disease development, expresses relevant drug targets and responds to repurposing candidates
Description	Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Its progressively expanding, fluid-filled renal cysts eventually lead to end-stage renal disease. Despite the relatively high prevalence, treatment options are currently limited to a single drug approved by the FDA and EMA. Here, we investigated human ADPKD patient-derived three-dimensional cyst cultures (3DCC) as an in vitro model for ADPKD and drug repurposing research. First, we analyzed the proteomes of 3DCC derived from healthy and diseased tissues. We then compared the protein expression profiles with those of reference tissues, mainly from the same patients. We quantified 290 proteins affecting drug disposition and proposed target proteins for drug treatment. Lastly, we investigated the functional response of the quantified target proteins after exposure to repurposing candidates in the 3DCC. Proteomic profiling of human 3DCC reflected previously reported pathophysiological alterations, including aberrant protein expression in inflammation and metabolic reprogramming. While the 3DCCs largely recapitulated the disease phenotype in vitro, drug transporter expression was reduced compared to in vivo conditions. Target proteins for proposed repurposing candidates showed similar expression in vitro and in tissues. Exposure to these repurposing candidates inhibited cyst swelling in vitro, supporting the suitability of the 3DCC for ADPKD drug screening. In summary, our results provide new insights into the ADPKD proteome and offer a starting point for further research to improve treatment options for affected individuals.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_06:12:11.837.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alina Meyer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-26 02:05:07	ID requested
⏵ 1	2025-05-06 06:12:12	announced

10.1111/CTS.70214;

submitter keyword: kidney, ADPKD, Global proteomics,human, 3D cyst cultures

Per Artursson
contact affiliation	Professor at Department of Pharmacy, Drug Delivery, Uppsala University (lab head)
contact email	per.artursson@farmaci.uu.se
lab head
Alina Meyer
contact affiliation	Department of Pharmacy, Uppsala University
contact email	alina.meyer@farmaci.uu.se
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/2025/05/PXD056281

PRIDE project URI

• PRIDE
  1. PXD056281
     1. Label: PRIDE project
     2. Name: A patient-derived 3D cyst model of polycystic kidney disease that mimics disease development, expresses relevant drug targets and responds to repurposing candidates