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Publication : Interaction between transcellular and paracellular water transport pathways through Aquaporin 5 and the tight junction complex.

First Author  Kawedia JD Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  9 Pages  3621-6
PubMed ID  17360692 Mgi Jnum  J:126077
Mgi Id  MGI:3760483 Doi  10.1073/pnas.0608384104
Citation  Kawedia JD, et al. (2007) Interaction between transcellular and paracellular water transport pathways through Aquaporin 5 and the tight junction complex. Proc Natl Acad Sci U S A 104(9):3621-6
abstractText  To investigate potential physiological interactions between the transcellular and paracellular pathways of water transport, we asked whether targeted deletion of Aquaporin 5 (AQP5), the major transcellular water transporter in salivary acinar cells, affected paracellular transport of 4-kDa FITC-labeled dextran (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 approximately 1.4-fold in glands from AQP5-/- mice, suggesting an alteration in the volume-sensing 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 gender-influenced molecular mechanism involving AQP5 that allows transcellular and paracellular routes of water transport to act in conjunction.
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