aquaporin expression contributes to human transurothelial permeability in vitro and is modulated by nacl水通道蛋白的表达有助于人类体外transurothelial渗透率和由氯化钠调制.pdfVIP
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aquaporin expression contributes to human transurothelial permeability in vitro and is modulated by nacl水通道蛋白的表达有助于人类体外transurothelial渗透率和由氯化钠调制
Aquaporin Expression Contributes to Human
Transurothelial Permeability In Vitro and Is Modulated
by NaCl
1¤ 1,2 1 1
Peter C. Rubenwolf , Nikolaos T. Georgopoulos , Lisa A. Kirkwood , Simon C. Baker ,
Jennifer Southgate1*
1Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York, United Kingdom, 2 Department of Chemical and Biological Sciences,
University of Huddersfield, Huddersfield, United Kingdom
Abstract
It is generally considered that the bladder is impervious and stores urine in unmodified form on account of the barrier
imposed by the highly-specialised uro-epithelial lining. However, recent evidence, including demonstration of aquaporin
(AQP) expression by human urothelium, suggests that urothelium may be able to modify urine content. Here we have we
applied functional assays to an in vitro-differentiated normal human urothelial cell culture system and examined both
whether AQP expression was responsive to changes in osmolality, and the effects of blocking AQP channels on water and
urea transport. AQP3 expression was up-regulated by increased osmolality, but only in response to NaCl. A small but similar
effect was seen with AQP9, but not AQP4 or AQP7. Differentiated urothelium revealed significant barrier function (mean TER
3862 V.cm2), with mean diffusive water and urea permeability coefficients of 6.33 61025 and 2.45 61025 cm/s, respectively.
AQP blockade with mercuric chloride resulted in decreased water and urea flux. The diffusive permeability of urothelial cell
sheets remained constant following conditioning in hyperosmotic NaCl, but there was a significant increase in water and
urea flux across an osmotic gradient. Taken coll
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