Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 9, Pages 3621-3626Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0608384104
Keywords
epithelium; fluid absorption and secretion
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Funding
- NIDCR NIH HHS [R01 DE013823, DE13823] Funding Source: Medline
- NIDDK NIH HHS [DK57552, R01 DK057552] Funding Source: Medline
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To investigate potential physiological interactions between the transcellular and paracellular pathways of water transport, we asked whether targeted deletion of Aquaporin 5 (AQPS), the major transcellular water transporter in salivary acinar cells, affected paracellular transport of 4-kDa FITC-labeled clextran (FITC-D), which is transported through the paracellular but not the transcellular route. After i.v. injection of FITC-D into either AQP5 wild-type or AQP5-/- mice and saliva collection for fixed time intervals, we show that the relative amount of FITC-D transported in the saliva of AQP5-/- mice is half that in matched AQP5+/+ mice, indicating a 2-fold decrease in permeability of the paracellular barrier in mice lacking AQP5. We also found a significant difference in the proportion of transcellular vs. paracellular transport between male and female mice. Freeze-fracture electron microscopy revealed an increase in the number of tight junction strands of both AQP5+/+ and AQP5-/- male*mice after pilocarpine stimulation but no change in strand number in female mice. Average acinar cell volume was increased by approximate to 1.4-fold in glands from AQP5-/- mice, suggesting an alteration in the volumesensing machinery of the cell. Western blots revealed that expression of Claudin-7, Claudin-3, and Occludin, critical proteins that regulate the permeability of the tight junction barrier, were significantly decreased in AQP5-/- compared with AQP5+/+ salivary glands. These findings reveal the existence of a genderinfluenced molecular mechanism involving AQP5 that allows transcellular and paracellular routes of water transport to act in conjunction.
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