{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T20:00:24Z","timestamp":1773259224867,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Children\u2019s Foundation Research Foundation, St. Jude Children\u2019s Research Hospital","award":["239283807"],"award-info":[{"award-number":["239283807"]}]},{"name":"Children\u2019s Foundation Research Foundation, St. Jude Children\u2019s Research Hospital","award":["431984000"],"award-info":[{"award-number":["431984000"]}]},{"name":"Children\u2019s Foundation Research Foundation, St. Jude Children\u2019s Research Hospital","award":["390939984"],"award-info":[{"award-number":["390939984"]}]},{"name":"the Federal Express Chair of Excellence to JJB, and the German Research Foundation (DFG)","award":["239283807"],"award-info":[{"award-number":["239283807"]}]},{"name":"the Federal Express Chair of Excellence to JJB, and the German Research Foundation (DFG)","award":["431984000"],"award-info":[{"award-number":["431984000"]}]},{"name":"the Federal Express Chair of Excellence to JJB, and the German Research Foundation (DFG)","award":["390939984"],"award-info":[{"award-number":["390939984"]}]},{"name":"Germany\u2019s Excellence Strategy","award":["239283807"],"award-info":[{"award-number":["239283807"]}]},{"name":"Germany\u2019s Excellence Strategy","award":["431984000"],"award-info":[{"award-number":["431984000"]}]},{"name":"Germany\u2019s Excellence Strategy","award":["390939984"],"award-info":[{"award-number":["390939984"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically intact cells to participate in the renal disease process. We used centrifugation and size exclusion chromatography to isolate the EVs for study. We characterized the EVs using tunable resistive pulse sensing, dynamic light scattering, transmission electron microscopy, and Western blot analysis. We performed EV trafficking studies using a dye approach in both tissue culture and in vivo studies. We have previously reported that loss of the Tsc2 gene significantly increased EV production and here demonstrate that the loss of the Pkd1 gene also significantly increases EV production. Using a cell culture system, we also show that loss of either the Tsc2 or Pkd1 gene results in EVs that exhibit an enhanced uptake by renal epithelial cells and a prolonged half-life. Loss of the primary cilia significantly reduces EV production in renal collecting duct cells. Cells that have a disrupted Pkd1 gene produce EVs that have altered kinetics and a prolonged half-life, possibly impacting the duration of the EV cargo effect on the recipient cell. These results demonstrate the interplay between primary cilia and EVs and support a role for EVs in polycystic kidney disease pathogenesis.<\/jats:p>","DOI":"10.3390\/biology11050709","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Single Gene Mutations in Pkd1 or Tsc2 Alter Extracellular Vesicle Production and Trafficking"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-6149","authenticated-orcid":false,"given":"Prashant","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Le Bonheur Children\u2019s Hospital, University of Tennessee Health Science Center, Memphis, TN 38103, USA"},{"name":"Children\u2019s Foundation Research Institute (CFRI), Le Bonheur Children\u2019s Hospital, Memphis, TN 38103, USA"},{"name":"US FDA National Center for Toxicological Research, Jefferson, AR 72079, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5891-4700","authenticated-orcid":false,"given":"Fahad","family":"Zadjali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Le Bonheur Children\u2019s Hospital, University of Tennessee Health Science Center, Memphis, TN 38103, USA"},{"name":"Children\u2019s Foundation Research Institute (CFRI), Le Bonheur Children\u2019s Hospital, Memphis, TN 38103, USA"},{"name":"Department of Clinical Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Le Bonheur Children\u2019s Hospital, University of Tennessee Health Science Center, Memphis, TN 38103, USA"},{"name":"Children\u2019s Foundation Research Institute (CFRI), Le Bonheur Children\u2019s Hospital, Memphis, TN 38103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"K\u00f6ttgen","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"CIBSS\u2014Centre for Integrative Biological Signaling Studies, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2842-6161","authenticated-orcid":false,"given":"Alexis","family":"Hofherr","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth W.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2925-7999","authenticated-orcid":false,"given":"Darshan","family":"Mehta","sequence":"additional","affiliation":[{"name":"US FDA National Center for Toxicological Research, Jefferson, AR 72079, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9685-9183","authenticated-orcid":false,"given":"John J.","family":"Bissler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Le Bonheur Children\u2019s Hospital, University of Tennessee Health Science Center, Memphis, TN 38103, USA"},{"name":"Children\u2019s Foundation Research Institute (CFRI), Le Bonheur Children\u2019s Hospital, Memphis, TN 38103, USA"},{"name":"Pediatric Medicine Department, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref_1","unstructured":"USRDS (2021, August 04). 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