Untersuchungen zur Rolle von Aquaporinen am Übergangsepithel der menschlichen Harnblase und deren potenzielle Bedeutung für die Pathogenese und Pharmakotherapie der Enuresis des Kindes- und Jugendalters
Zusammenfassung der Projektergebnisse
This is the first study to demonstrate that AQP water channels are expressed by human urothelium. Our results provide evidence that, at least in vitro, expression of AQP 3 and 9 are regulated by osmolality, which is supportive of our hypothesis, that urothelium may be capable of reabsorbing water in response to the body’s hydration status. Moreover, our findings indicate that expression and localisation of AQP 3 are associated with urothelial cyto-differentiation, suggesting a potential role in the establishment of cell-cell contacts and cell polarity within complex epithelia. Functional assays revealed a low, but finite permeablity of cultured urothelium to water and urea, which was reproducibly reduced by AQP inhibition (HgCl2). These findings challenge the traditional concept of the urinary tract as an impermeable transit and storage unit and and are supportive of our hypothesis that the lower urinary tract may be able to modify the composition and volume of urine. From a clinical point of view, expression of AQPs by human urothelium may have important implications on the development and maintainance of urinary continence, as recently suggested by a study into the pathophysiology of monosymptomatic enuresis nocturna. Taken together, this work has generated novel research findings, opening up the potential for future studies into the clinical relevance of AQP expression in human urothelium, such as its role in dysfunctional bladder syndroms and congenital malformations of the urinary tract.
Projektbezogene Publikationen (Auswahl)
- Investigation of water transport across human bladder epithelium in relation to its role in nocturnal enuresis. 4th HYMS conference, York Racecourse, 8th March 2007
Peter Rubenwolf, Lisa Clements, Sally Feather, David FM Thomas, Philip Holland and Jenny Southgate
- A biomimetic tissue from cultured human urothelial cells: a model to explore aquaporin-mediated water and solute transport across urothelium. Annual Meeting of the British Association of Urological Surgeons (BAUS), Section of Academic Urology, Royal College of Surgeons, London, 11th January 2008
Peter Rubenwolf, Lisa Clements, Sally Feather, David FM Thomas, Philip Holland and Jenny Southgate
- Expression and potential clinical relevance of aquaporins in normal human urothelium. Annual Meeting of the EAU (European Association of Urology) in Milan, 26-29 March 2008
Peter Rubenwolf, Lisa Clements, Sally Feather, David FM Thomas, Philip Holland and Jenny Southgate
- Expression of aquaporins in human urothelium. Annual Meeting of the ESPU (European Society of Pediatric Urologists) in Nice, 23-26 April 2008
Peter Rubenwolf, Lisa Clements, Sally Feather, David FM Thomas, Philip Holland and Jenny Southgate
