{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:38:38Z","timestamp":1793716718268,"version":"4.6.1"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,4,10]]},"abstract":"<jats:p>\n                    Cardiovascular complications such as hypertension are a continuous concern in patients with autosomal dominant polycystic kidney disease (ADPKD). The\n                    <jats:italic>PKD2<\/jats:italic>\n                    encoding for polycystin-2 is mutated in \u224815% of ADPKD patients. Here, we show that polycystin-2 is localized to the cilia of mouse and human vascular endothelial cells. We demonstrate that the normal expression level and localization of polycystin-2 to cilia is required for the endothelial cilia to sense fluid shear stress through a complex biochemical cascade, involving calcium, calmodulin, Akt\/PKB, and protein kinase C. In response to fluid shear stress, mouse endothelial cells with knockdown or knockout of\n                    <jats:italic>Pkd2<\/jats:italic>\n                    lose the ability to generate nitric oxide (NO). Consistent with mouse data, endothelial cells generated from ADPKD patients do not show polycystin-2 in the cilia and are unable to sense fluid flow. In the isolated artery, we further show that ciliary polycystin-2 responds specifically to shear stress and not to mechanical stretch, a pressurized biomechanical force that involves purinergic receptor activation. We propose a new role for polycystin-2 in transmitting extracellular shear stress to intracellular NO biosynthesis. Thus, aberrant expression or localization of polycystin-2 to cilia could promote high blood pressure because of inability to synthesize NO in response to an increase in shear stress (blood flow).\n                  <\/jats:p>","DOI":"10.1161\/circresaha.108.192765","type":"journal-article","created":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T00:09:14Z","timestamp":1236298154000},"page":"860-869","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":295,"title":["Ciliary Polycystin-2 Is a Mechanosensitive Calcium Channel Involved in Nitric Oxide Signaling Cascades"],"prefix":"10.1161","volume":"104","author":[{"given":"Wissam A.","family":"AbouAlaiwi","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R.","family":"Mell","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Jones","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shobha","family":"Ratnam","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Kolb","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surya M.","family":"Nauli","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (W.A.A., M.T., B.R.M., T.J.J., S.M.N.), College of Pharmacy; and Department of Medicine (S.R., S.M.N.), College of Medicine, University of Toledo, Ohio; and Department of Pediatrics (R.J.K.), Medical University of South Carolina, Charleston. Present address for T.J.J.: Pharmaceutical Sciences, Northeastern Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201162"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60601-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00989.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)03495-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/71724"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000132462"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1211"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65428-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35050128"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1076"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00511-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.710111"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6965"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1071524"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81793-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00122.2003"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1999.19430335.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1181"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20069"},{"key":"e_1_3_3_20_2","first-page":"4451","volume":"13","year":"2008","unstructured":"Kolb RJ, Nauli SM. Ciliary dysfunction in polycystic kidney disease: an emerging model with polarizing potential. Front Biosci. 2008; 13: 4451\u20134466.","journal-title":"Front Biosci"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.040403.101353"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21472"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005080830"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00285.2006"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.10.7615166"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.108.192765","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:39:43Z","timestamp":1715557183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.108.192765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,10]]},"references-count":25,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,4,10]]}},"alternative-id":["10.1161\/CIRCRESAHA.108.192765"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.108.192765","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1160667.622059","asserted-by":"object"}]},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,10]]},"assertion":[{"value":"2009-03-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}