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Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst\u2010lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RC\/RC<\/jats:italic>\n                    <\/jats:sup>\n                    mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin\u20101, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin\u20101 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin\u20101 function with probenecid can be used to attenuate ADPKD development. Renal function in male and female\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RC\/RC<\/jats:italic>\n                    <\/jats:sup>\n                    and control mice was monitored between 9 and 20\u2009months of age. To test the therapeutic effects of probenecid (a uricosuric agent and a pannexin\u20101 blocker), osmotic minipumps were implanted in male and female\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RC\/RC<\/jats:italic>\n                    <\/jats:sup>\n                    mice, and probenecid or vehicle was administered for 42\u2009days until 1\u2009year of age. Probenecid treatment improved glomerular filtration rates and slowed renal cyst formation in male mice (as shown in histopathology). The mechanistic effects of probenecid on sodium reabsorption and fluid transport were tested on polarized mpkCCD\n                    <jats:sub>cl4<\/jats:sub>\n                    cells subjected to short\u2010circuit current measurements, and in 3D cysts grown in Matrigel. In the mpkCCD\n                    <jats:sub>cl4<\/jats:sub>\n                    epithelial cell line, probenecid elicited higher ENaC currents and attenuated in vitro cyst formation, indicating lower sodium and less fluid retention in the cysts. Our studies open new avenues of research into targeting pannexin\u20101 in ADPKD pathology.\n                  <\/jats:p>","DOI":"10.14814\/phy2.15652","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T21:24:10Z","timestamp":1680816250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Probenecid slows disease progression in a murine model of autosomal dominant polycystic kidney disease"],"prefix":"10.14814","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4707-902X","authenticated-orcid":false,"given":"Sergey N.","family":"Arkhipov","sequence":"first","affiliation":[{"name":"Division of Hypertension and Vascular Research Henry Ford Health  Detroit Michigan USA"},{"name":"Department of Physiology Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D'Anna 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