dc.contributor.author |
Fong, Shelley |
en |
dc.contributor.author |
Chiorini, JA |
en |
dc.contributor.author |
Sneyd, A |
en |
dc.contributor.author |
Suresh, Vinod |
en |
dc.date.accessioned |
2017-09-24T20:34:17Z |
en |
dc.date.issued |
2017-02 |
en |
dc.identifier.citation |
American Journal of Physiology - Gastrointestinal and Liver Physiology 312(2):G153-G163 Feb 2017 |
en |
dc.identifier.issn |
0193-1857 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/35752 |
en |
dc.description.abstract |
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.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. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.publisher |
American Physiological Society |
en |
dc.relation.ispartofseries |
American Journal of Physiology - Gastrointestinal and Liver Physiology |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Parotid Gland |
en |
dc.subject |
Saliva |
en |
dc.subject |
Animals |
en |
dc.subject |
Humans |
en |
dc.subject |
Transfection |
en |
dc.subject |
Gene Expression Regulation |
en |
dc.subject |
Ion Transport |
en |
dc.subject |
Models, Biological |
en |
dc.subject |
Computer Simulation |
en |
dc.subject |
Aquaporin 1 |
en |
dc.subject |
Transcriptome |
en |
dc.title |
Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1 |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1152/ajpgi.00374.2016 |
en |
pubs.issue |
2 |
en |
pubs.begin-page |
G153 |
en |
pubs.volume |
312 |
en |
dc.rights.holder |
Copyright: American Physiological Society |
en |
dc.identifier.pmid |
27932503 |
en |
pubs.end-page |
G163 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
603720 |
en |
pubs.org-id |
Bioengineering Institute |
en |
pubs.org-id |
ABI Associates |
en |
pubs.org-id |
Engineering |
en |
pubs.org-id |
Engineering Science |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Mathematics |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1522-1547 |
en |
pubs.record-created-at-source-date |
2017-09-25 |
en |
pubs.dimensions-id |
27932503 |
en |