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Although the disease remains incompletely understood, one of the factors associated with ADPKD progression is the release of nucleotides (including ATP), which can initiate autocrine or paracrine purinergic signaling by binding to their receptors. Recently, we and others have shown that increased extracellular vesicle (EVs) release from\n                    <jats:italic>PKD1<\/jats:italic>\n                    knockout cells can stimulate cyst growth through effects on recipient cells. Given that EVs are an important communicator between different nephron segments, we hypothesize that EVs released from\n                    <jats:italic>PKD1<\/jats:italic>\n                    knockout distal convoluted tubule (DCT) cells can stimulate cyst growth in the downstream collecting duct (CD). Here, we show that administration of EVs derived from\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mouse distal convoluted tubule (mDCT15) cells result in a significant increase in extracellular ATP release from\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mouse inner medullary collecting duct (iMCD3) cells. In addition, exposure of\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    iMCD3 cells to EVs derived from\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mDCT15 cells led to an increase in the phosphorylation of the serine\/threonine\u2010specific protein Akt, suggesting activation of proliferative pathways. Finally, the exposure of iMCD3\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    cells to mDCT15\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    EVs increased cyst size in Matrigel. These findings indicate that EVs could be involved in intersegmental communication between the distal convoluted tubule and the collecting duct and potentially stimulate cyst growth.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300490r","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T11:10:18Z","timestamp":1685445018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Extracellular vesicles contribute to early cyst development in autosomal dominant polycystic kidney disease by cell\u2010to\u2010cell communication"],"prefix":"10.1096","volume":"37","author":[{"given":"Valentina","family":"Carotti","sequence":"first","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-4021","authenticated-orcid":false,"given":"Wouter H.","family":"van Megen","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4168-9396","authenticated-orcid":false,"given":"Juan P.","family":"Rigalli","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric R.","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2289-9179","authenticated-orcid":false,"given":"Vera","family":"Sommers","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luco","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Electron Microscopy Center, Radboudumc Technology Center Microscopy Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-195X","authenticated-orcid":false,"given":"Nico","family":"Sommerdijk","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Electron Microscopy Center, Radboudumc Technology Center Microscopy Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-7143","authenticated-orcid":false,"given":"Dorien J. 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