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PXD056281

PXD056281 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA patient-derived 3D cyst model of polycystic kidney disease that mimics disease development, expresses relevant drug targets and responds to repurposing candidates
DescriptionAutosomal 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.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_06:12:11.837.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlina Meyer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-26 02:05:07ID requested
12025-05-06 06:12:12announced
Publication List
10.1111/CTS.70214;
Keyword List
submitter keyword: kidney, ADPKD, Global proteomics,human, 3D cyst cultures
Contact List
Per Artursson
contact affiliationProfessor at Department of Pharmacy, Drug Delivery, Uppsala University (lab head)
contact emailper.artursson@farmaci.uu.se
lab head
Alina Meyer
contact affiliationDepartment of Pharmacy, Uppsala University
contact emailalina.meyer@farmaci.uu.se
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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