{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:09:28Z","timestamp":1779152968381,"version":"3.51.4"},"reference-count":43,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH HIDDK","award":["R01 DK117650,RO1-DK29857,R01 DK54053,P30DK079310"],"award-info":[{"award-number":["R01 DK117650,RO1-DK29857,R01 DK54053,P30DK079310"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,24]]},"abstract":"<jats:p>\n                    Flow-activated Na\n                    <jats:sup>+<\/jats:sup>\n                    and HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2013<\/jats:sup>\n                    transport in kidney proximal tubules (PT) underlies relatively constant fractional reabsorption during changes in glomerular filtration rate (GFR) or glomerulotubular balance (GTB). In view of hypothesized connections of epithelial cilia to flow sensing, we examined flow-activated transport in 3 polycystic kidney disease\u2013related mouse models based on inducible conditional KO of\n                    <jats:italic>Pkd1<\/jats:italic>\n                    ,\n                    <jats:italic>Pkd2<\/jats:italic>\n                    , and\n                    <jats:italic>Kif3a<\/jats:italic>\n                    . PTs were harvested from mice after gene inactivation but prior to cyst formation, and flow-mediated PT transport was measured. We confirm that higher flow increased both Na\n                    <jats:sup>+<\/jats:sup>\n                    and HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2013<\/jats:sup>\n                    absorption in control mice, and we observed that this flow effect was preserved in PTs of\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Kif3a\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. However, flow activation was absent in\n                    <jats:italic>Pkd2<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    and\n                    <jats:italic>\n                      Pkd2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    PT. In heterozygous (\n                    <jats:italic>\n                      Pkd2\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice, a dopamine receptor 1 (DA1) antagonist (SCH23390) restored transport flow sensitivity. When given chronically, this same antagonist reduced renal cyst formation in\n                    <jats:italic>\n                      Pkd2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      ,\n                    <\/jats:italic>\n                    as evidenced by reduced kidney weight, BUN, and the cystic index, when compared with untreated mice. In contrast, SCH23390 did not prevent cyst formation in\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These results indicate that\n                    <jats:italic>Pkd2<\/jats:italic>\n                    is necessary for normal GTB and that restoration of flow-activated transport by DA1 antagonist can slow renal cyst formation in\n                    <jats:italic>\n                      Pkd2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.146041","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T12:05:09Z","timestamp":1619093109000},"source":"Crossref","is-referenced-by-count":9,"title":["Restoration of proximal tubule flow\u2013activated transport prevents cyst growth in polycystic kidney disease"],"prefix":"10.1172","volume":"6","author":[{"given":"Zhaopeng","family":"Du","sequence":"first","affiliation":[{"name":"Department of C&M Physiology 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