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Differentiation potential of urothelium from patients with benign bladder dysfunction

Southgate, J., Varley, C.L., Garthwaite, M.A.E., Hinley, J., Marsh, F., Stahlschmidt, J., Trejdosiewicz, L.K. and Eardley, I. (2007) Differentiation potential of urothelium from patients with benign bladder dysfunction. BJU International, 99 (6). pp. 1506-1516. ISSN 1464-4096

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OBJECTIVE : To develop a novel in vitro approach to test the hypothesis that failure of urothelial differentiation underlies the aetiopathology of interstitial cystitis (IC), where there is evidence of compromised urinary barrier function, as benign dysfunctional bladder disease encompass several poorly understood clinically defined conditions, including IC, idiopathic detrusor overactivity (IDO) and stress urinary incontinence (SUI).

MATERIALS AND METHODS : Biopsy-derived urothelial cells from dysfunctional bladder biopsies were propagated as finite cell lines and examined for their capacity to differentiate in vitro, as assessed by the acquisition of a transitional cell morphology, a switch from a cytokeratin (CK)13lo/CK14hi to a CK13hi/CK14lo phenotype, expression of claudin 3, 4 and 5 proteins, and induction of uroplakin gene transcription.

RESULTS : Two of 12 SUI cell lines showed early senescent changes in culture and were not characterized further; one of seven IC, one of five IDO and a further three SUI cell lines had some evidence of senescence at passage 3. Of the seven IC-derived cell lines, four showed a near normal range of differentiation-associated responses, but the remainder showed little or no response. Most IDO cell lines (four of five) showed a normal differentiation response, but at least three of the 10 SUI cell lines showed some compromise of differentiation potential.

CONCLUSION : This study supports the existence of a subset of patients with IC in whom a failure of urothelial cytodifferentiation might contribute to the disease, and provides a novel platform for investigating the cell biology of urothelium from SUI and other benign dysfunctional conditions.

Item Type: Article
Copyright, Publisher and Additional Information: Open access copy available from the journal web site.
Keywords: bladder, claudin, differentiation, idiopathic detrusor overactivity, interstitial cystitis, stress urinary incontinence, uroplakin
Institution: The University of Leeds, The University of York
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds)
The University of York > Biology (York)
Depositing User: Open Access From Journal
Date Deposited: 23 Dec 2008 14:00
Last Modified: 23 Dec 2008 14:00
Published Version: http://dx.doi.org/10.1111/j.1464-410X.2007.06795.x
Status: Published
Publisher: Wiley-Blackwell
Refereed: Yes
Identification Number: 10.1111/j.1464-410X.2007.06795.x
URI: http://eprints.whiterose.ac.uk/id/eprint/5048

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