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Differentiation potential of urothelium from patients with benign bladder dysfunction
Author(s) -
Southgate Jennifer,
Varley Claire L.,
Garthwaite Mary A.E.,
Hinley Jennifer,
Marsh Fiona,
Stahlschmidt Jens,
Trejdosiewicz Ludwik K.,
Eardley Ian
Publication year - 2007
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2007.06795.x
Subject(s) - urothelium , urothelial cell , cytokeratin , cell culture , urinary bladder , cell , cancer research , medicine , pathology , biology , microbiology and biotechnology , immunohistochemistry , genetics
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)13 lo /CK14 hi to a CK13 hi /CK14 lo 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.