{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:30:12Z","timestamp":1772155812280,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,3,19]],"date-time":"2018-03-19T00:00:00Z","timestamp":1521417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK095029"],"award-info":[{"award-number":["DK095029"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01\u2010DK081579"],"award-info":[{"award-number":["R01\u2010DK081579"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17GRNT33660488"],"award-info":[{"award-number":["17GRNT33660488"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n                    Autosomal\u2010dominant polycystic kidney disease (ADPKD) is a devastating disorder that is charac\u2010terized by a progressive decline in renal function as a result of the development of fluid\u2010filled cysts. Defective flow\u2010mediated [Ca\n                    <jats:sup>2<\/jats:sup>\n                    +]\n                    <jats:sub>i<\/jats:sub>\n                    responses and disrupted [Ca\n                    <jats:sup>2<\/jats:sup>\n                    +]\n                    <jats:sub>i<\/jats:sub>\n                    homeostasis have been repeatedly associated with cyst progression in ADPKD. We have previously demonstrated that the transient receptor potential vanilloid type 4 (TRPV4) channel is imperative for flow\u2010mediated [Ca\n                    <jats:sup>2<\/jats:sup>\n                    +]\n                    <jats:sub>i<\/jats:sub>\n                    responses in murine distal renal tubule cells. To determine whether compromised TRPV4 function contributes to aberrant Ca\n                    <jats:sup>2+<\/jats:sup>\n                    regulation in ADPKD, we assessed TRPV4 function in primary cells that were cultured from ADPKD and normal human kidneys (NHKs). Single\u2010channel TRPV4 activity and TRPV4\u2010dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influxes were drastically reduced in ADPKD cells, which correlated with distorted [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling. Whereas total TRPV4 protein levels were comparable in NHK and ADPKD cells, we detected a marked decrease in TRPV4 glycosylation in ADPKD cells. Tunicamycin\u2010induced deglycosylation inhibited TRPV4 activity and compromised [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling in NHK cells. Overall, we demonstrate that TRPV4 glycosylation and channel activity are diminished in human ADPKD cells compared with NHK cells, and that this contributes significantly to the distorted [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    dy\u2010namics. We propose that TRPV4 stimulation may be beneficial for restoring [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    homeostasis in cyst cells, thereby interfering with ADPKD progression.\u2014Tomilin, V., Reif, G. A., Zaika, O., Wallace, D. P., Pochynyuk, O. Deficient transient receptor potential vanilloid type 4 function contributes to compromised [Ca2+]i ho\u2010meostasis in human autosomal\u2010dominant polycystic kidney disease cells.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 32, 4612\u20104623 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701535rr","type":"journal-article","created":{"date-parts":[[2018,3,19]],"date-time":"2018-03-19T13:50:34Z","timestamp":1521467434000},"page":"4612-4623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Deficient transient receptor potential vanilloid type 4 function contributes to compromised [Ca\n                    <sup>2+<\/sup>\n                    ] homeostasis in human autosomal\u2010dominant polycystic kidney disease cells"],"prefix":"10.1096","volume":"32","author":[{"given":"Viktor","family":"Tomilin","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center at Houston Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail A.","family":"Reif","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Zaika","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center at Houston Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleh","family":"Pochynyuk","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center at Houston Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.59"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573402111309010002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.60.101707.125712"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60601-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0070"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nrneph.2011.196","article-title":"Polycystic kidney disease in 2011: connecting the dots toward a polycystic kidney disease therapy","volume":"8","author":"Torres V. 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