{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:42:10Z","timestamp":1790642530482,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,5]]},"abstract":"\n Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in\n Pde1<\/jats:italic>\n - or\n Pde3<\/jats:italic>\n -knockout mice on the\n Pkd2<\/jats:italic>\n \u2212\/WS25<\/jats:sup>\n background (WS25 is an unstable\n Pkd2<\/jats:italic>\n allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (\n PDE1<\/jats:italic>\n ), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) \u2013driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In\n Pkd2<\/jats:italic>\n \u2212\/WS25<\/jats:sup>\n mice, knockout of\n Pde1a<\/jats:italic>\n ,\n Pde1c<\/jats:italic>\n , or\n Pde3a<\/jats:italic>\n but not of\n Pde1b<\/jats:italic>\n or\n Pde3b<\/jats:italic>\n aggravated the development of PKD and was associated with higher levels of protein kinase A\u2013phosphorylated (Ser133) cAMP\u2013responsive binding protein (P-CREB), activating transcription factor-1, and CREB\u2013induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in\n Pkd2\u2212\/<\/jats:italic>\n WS25<\/jats:sup>\n ;\n Pde1a<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ,\n Pkd2\u2212<\/jats:italic>\n \/WS25<\/jats:sup>\n ;\n Pde1c<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n , and\n Pkd2\u2212\/<\/jats:italic>\n WS25<\/jats:sup>\n ;\n Pde3a<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in\n Pkd2<\/jats:italic>\n \u2212\/WS25<\/jats:sup>\n ;\n Pde3a<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (\n PDE1A<\/jats:italic>\n and\n PDE1C<\/jats:italic>\n ) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR\u2013driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.\n <\/jats:p>","DOI":"10.1681\/asn.2015010057","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T22:10:12Z","timestamp":1442355012000},"page":"1312-1320","source":"Crossref","is-referenced-by-count":39,"title":["Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies"],"prefix":"10.1681","volume":"27","author":[{"given":"Hong","family":"Ye","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline R.","family":"Sussman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Hopp","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Irazabal","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Bakeberg","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wells B.","family":"LaRiviere","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent C.","family":"Manganiello","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles V.","family":"Vorhees","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology, Cincinnati Children\u2019s Research Foundation and University of Cincinnati, Cincinnati, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Deursen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Ward","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente E.","family":"Torres","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,9,15]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev.med.60.101707.125712","article-title":"Polycystic kidney disease.","volume":"60","author":"Harris","year":"2009","journal-title":"Annu Rev Med"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrneph.2015.39","article-title":"Vasopressin and disruption of 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