Differentiation potential of urothelium from patients with benign bladder dysfunction.
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).


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.


CONCLUSIONS
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.
Southgate
Jennifer
J
Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, York, UK. js35@york.ac.uk
Varley
Claire L
CL
Garthwaite
Mary A E
MA
Hinley
Jennifer
J
Marsh
Fiona
F
Stahlschmidt
Jens
J
Trejdosiewicz
Ludwik K
LK
Eardley
Ian
I
D001706:Biopsy / Q000379:methods; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D053535:Keratin-13 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D014550:Urinary Incontinence, Stress / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
D053535:Keratin-13