Differentiation potential of urothelium from patients with benign bladder dysfunction

Jennifer Southgate; Claire L. Varley; Mary A. E. Garthwaite; Jennifer Hinley; Fiona Marsh; Jens Stahlschmidt; Ludwik K. Trejdosiewicz; Ian Eardley

doi:10.1111/j.1464-410X.2007.06795.x

Differentiation potential of urothelium from patients with benign bladder dysfunction

Jennifer Southgate, Claire L. Varley, Mary A. E. Garthwaite, Jennifer Hinley, Fiona Marsh, Jens Stahlschmidt, Ludwik K. Trejdosiewicz, Ian Eardley

Research output: Contribution to journal › Article › peer-review

Abstract

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).

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.

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.

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.

Original language	English
Pages (from-to)	1506-1516
Number of pages	11
Journal	BJU International
Volume	99
Issue number	6
DOIs	https://doi.org/10.1111/j.1464-410X.2007.06795.x
Publication status	Published - Jun 2007

Bibliographical note

Open access copy available from the journal web site.

Keywords

bladder
claudin
differentiation
idiopathic detrusor overactivity
interstitial cystitis
stress urinary incontinence
uroplakin
INTERSTITIAL CYSTITIS
URINARY-TRACT
PPAR-GAMMA
IN-VITRO
CELLS
EXPRESSION
PROLIFERATION

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10.1111/j.1464-410X.2007.06795.x

http://dx.doi.org/10.1111/j.1464-410X.2007.06795.x

Cite this

@article{c55f985472ac4ec183d67dfc27967c52,

title = "Differentiation potential of urothelium from patients with benign bladder dysfunction",

abstract = "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).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.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.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.",

keywords = "bladder, claudin, differentiation, idiopathic detrusor overactivity, interstitial cystitis, stress urinary incontinence, uroplakin, INTERSTITIAL CYSTITIS, URINARY-TRACT, PPAR-GAMMA, IN-VITRO, CELLS, EXPRESSION, PROLIFERATION",

author = "Jennifer Southgate and Varley, {Claire L.} and Garthwaite, {Mary A. E.} and Jennifer Hinley and Fiona Marsh and Jens Stahlschmidt and Trejdosiewicz, {Ludwik K.} and Ian Eardley",

note = "Open access copy available from the journal web site.",

year = "2007",

month = jun,

doi = "10.1111/j.1464-410X.2007.06795.x",

language = "English",

volume = "99",

pages = "1506--1516",

journal = "BJU International",

issn = "1464-4096",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Differentiation potential of urothelium from patients with benign bladder dysfunction

AU - Southgate, Jennifer

AU - Varley, Claire L.

AU - Garthwaite, Mary A. E.

AU - Hinley, Jennifer

AU - Marsh, Fiona

AU - Stahlschmidt, Jens

AU - Trejdosiewicz, Ludwik K.

AU - Eardley, Ian

N1 - Open access copy available from the journal web site.

PY - 2007/6

Y1 - 2007/6

N2 - 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).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.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.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.

AB - 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).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.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.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.

KW - bladder

KW - claudin

KW - differentiation

KW - idiopathic detrusor overactivity

KW - interstitial cystitis

KW - stress urinary incontinence

KW - uroplakin

KW - INTERSTITIAL CYSTITIS

KW - URINARY-TRACT

KW - PPAR-GAMMA

KW - IN-VITRO

KW - CELLS

KW - EXPRESSION

KW - PROLIFERATION

U2 - 10.1111/j.1464-410X.2007.06795.x

DO - 10.1111/j.1464-410X.2007.06795.x

M3 - Article

SN - 1464-4096

VL - 99

SP - 1506

EP - 1516

JO - BJU International

JF - BJU International

IS - 6

ER -