{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:46:17Z","timestamp":1792280777782,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Its progressively expanding, fluid\u2010filled renal cysts eventually lead to end\u2010stage 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\u2010derived three\u2010dimensional cyst cultures (3DCC) as an in\u00a0vitro 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\u00a0vitro, drug transporter expression was reduced compared to in\u00a0vivo conditions. Target proteins for proposed repurposing candidates showed similar expression in\u00a0vitro and in tissues. Exposure to these repurposing candidates inhibited cyst swelling in\u00a0vitro, 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.<\/jats:p>","DOI":"10.1111\/cts.70214","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T01:41:46Z","timestamp":1744767706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Patient\u2010Derived\n                    <scp>3D<\/scp>\n                    Cyst Model of Polycystic Kidney Disease That Mimics Disease Development and Responds to Repurposing Candidates"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2097-6295","authenticated-orcid":false,"given":"Alina","family":"Hartwig","sequence":"first","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-992X","authenticated-orcid":false,"given":"Bola","family":"Khalil","sequence":"additional","affiliation":[{"name":"In Silico Discovery, J&amp;J Innovative Medicine  Beerse Belgium"},{"name":"Division of Medicinal Chemistry Leiden Academic Centre for Drug Research  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5433-0757","authenticated-orcid":false,"given":"Margarita","family":"Iljin","sequence":"additional","affiliation":[{"name":"Crown Bioscience Netherlands B.V  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"Bange","sequence":"additional","affiliation":[{"name":"Crown Bioscience Netherlands B.V  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4562-9086","authenticated-orcid":false,"given":"Leo S.","family":"Price","sequence":"additional","affiliation":[{"name":"Crown Bioscience Netherlands B.V  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5892-3778","authenticated-orcid":false,"given":"Natalia","family":"Dyubankova","sequence":"additional","affiliation":[{"name":"In Silico Discovery, J&amp;J Innovative Medicine  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-1817","authenticated-orcid":false,"given":"Gerard J. 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