{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:03:55Z","timestamp":1773425035789,"version":"3.50.1"},"reference-count":44,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/501100001509","name":"Royal Society of New Zealand","doi-asserted-by":"publisher","award":["UOA1411"],"award-info":[{"award-number":["UOA1411"]}],"id":[{"id":"10.13039\/501100001509","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:p> Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemistry of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates. Using a baseline set of parameters, the model reproduces the data for the irradiated, non-AQP1-transfected case. We propose three scenarios which may have occurred after transfection, which differ in the location of the AQP1 gene. The first scenario places AQP1 within nonsecretory cells, and requires that epithelial sodium channel (ENaC) expression is greatly reduced (1.3% of baseline), and ductal bicarbonate concentration is increased from 40.6 to 137.0 mM, to drive water secretion into the duct. The second scenario introduces the AQP1 gene into all ductal cells. The final scenario has AQP1 primarily in the proximal duct cells which secrete water under baseline conditions. We find the change in the remaining cells includes a 95.8% reduction in ENaC expression, enabling us to reproduce all experimental ionic concentrations within 9 mM. These findings provide a mechanistic basis for the observations and will guide the further development of gene transfer therapy for salivary hypofunction. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Following transfection of aquaporin into the parotid ducts of minipigs with salivary hypofunction, the resulting increase in salivary flow rates contradicts current understanding of ductal fluid transport. We show that the change in saliva electrochemistry and flow rate can be explained by changes in expression of ion transporters in the ductal cell membranes, using a mathematical model replicating a single parotid duct. <\/jats:p>","DOI":"10.1152\/ajpgi.00374.2016","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T22:45:18Z","timestamp":1481237118000},"page":"G153-G163","source":"Crossref","is-referenced-by-count":10,"title":["Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1"],"prefix":"10.1152","volume":"312","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8610-1088","authenticated-orcid":false,"given":"Shelley","family":"Fong","sequence":"first","affiliation":[{"name":"Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Chiorini","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Sneyd","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Auckland, Auckland, New Zealand; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod","family":"Suresh","sequence":"additional","affiliation":[{"name":"Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand;"},{"name":"Department of Engineering Science, University of Auckland, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.273.3.F473"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.2.C633"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001520402"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.183541"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2014.01.005"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(81)90444-2"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.070557"},{"key":"B8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.5005\/jcdp-9-3-72","volume":"9","author":"de Almeida PV","year":"2008","journal-title":"J Contemp Dent Pract"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(05)80076-0"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.128"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2007.04.021"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00421.2001"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.102.4.601"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1113\/JP271378"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20006"},{"key":"B16","volume-title":"Mathematical Physiology: I: Cellular Physiology","author":"Keener J","year":"2008"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1021\/ed037p14"},{"key":"B18","volume-title":"Human Microscopic Anatomy: An Atlas for Students of Medicine and Biology","author":"Krstic RV","year":"2013"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2011"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510380414"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008548200"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-011-9413-3"},{"key":"B23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1152\/ajplegacy.1973.225.1.18","volume":"225","author":"Mangos JA","year":"1973","journal-title":"Am J Physiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.12018"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-002-1036-2"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00511.2007"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3366-2_5"},{"key":"B28","unstructured":"Palk, L. A Mathematical Study of the Role of Calcium in the Regulation of Saliva Secretion (PhD thesis). Auckland, New Zealand: University of Auckland, 2012."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2012"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001080306"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00364.2011"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5340"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1976.40.5.752"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070260103"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.1.8.585"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.154468"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2004.01.010"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2014.06.017"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/BF00580964"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2005.10.001"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051170303"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.10815.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.dmfr.4600336"},{"key":"B44","volume-title":"Comprehensive Human Physiology: From Cellular Mechanisms to Integration","author":"Young J A","year":"1996"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00374.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T01:55:31Z","timestamp":1567994131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00374.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,1]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2,1]]}},"alternative-id":["10.1152\/ajpgi.00374.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00374.2016","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,1]]}}}