Urothelial differentiation in chronically urine-deprived bladders of patients with end-stage renal disease

J Stahlschmidt; C L Varley; G Toogood; P J Selby; J Southgate

Urothelial differentiation in chronically urine-deprived bladders of patients with end-stage renal disease

J Stahlschmidt, C L Varley, G Toogood, P J Selby, J Southgate

Jack Birch Unit

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

Abstract

Background. It is unknown whether normal bladder voiding function, or soluble factors present in urine, contribute to the maturation and maintenance of the differentiated state of the uroepithelial cell lining of the lower urinary tract.

Methods. We used the urothelium of anuric patients on long-term hemodialysis, sampled at the time of renal transplantation, to investigate the expression of urothelial differentiation-associated antigens, including uroplakins (UPIa, UPIb, UPII, and UPIIIa), cytokeratin isotypes (CK7, CK8, CK13, CK14, CK17, CK18, and CK20), nuclear hormone receptors [peroxisome proliferators activated receptor-gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha)], and a cell cycle marker (Ki-67). To determine whether urinary metabolites of the arachidonic pathway could induce urothelial differentiation, cultured normal human urothelial (NHU) cells were treated with 15-deoxy-Delta 12, 14-prostaglandin J(2) (15d-PGJ(2)) and prostaglandin J(2) (PGJ(2)). The expression levels of the markers of differentiation, the uroplakins, were assessed by ribonuclease protection assay.

Results. When compared in a blinded analysis against control normal urothelium, no significant changes were found in the expression or localization patterns of any of the antigens studied in the anuric patients. Furthermore, neither 15d-PGJ(2) nor PGJ(2) were able to induce expression of the UPII gene in NHU cells, in contrast to cultures exposed to the pharmacologic PPAR-gamma agonist, troglitazone.

Conclusion. These data provide prima facie evidence that exogenous urine-derived factors do not modulate the differentiation program in urothelium, suggesting that other urothelial- or serum-derived factors are likely to be involved. These findings are important in understanding post-developmental maturation and functional relationships in urologic tissues of the adult organism.

Original language	English
Pages (from-to)	1032-1040
Number of pages	9
Journal	Kidney international
Volume	68
Issue number	3
Publication status	Published - Sept 2005

Keywords

urothelium
PPAR
differentiation
anuria
prostaglandin
bladder
PROLIFERATOR-ACTIVATED RECEPTOR
TRANSITIONAL-CELL CARCINOMA
UROPLAKIN GENE-EXPRESSION
PPAR-GAMMA
15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2)
HETERODIMER FORMATION
MEMBRANE-PROTEINS
HUMAN TISSUES
IN-VITRO
LIGANDS

Cite this

@article{3d6148a6b23d48099b00fdcf656b5471,

title = "Urothelial differentiation in chronically urine-deprived bladders of patients with end-stage renal disease",

abstract = "Background. It is unknown whether normal bladder voiding function, or soluble factors present in urine, contribute to the maturation and maintenance of the differentiated state of the uroepithelial cell lining of the lower urinary tract.Methods. We used the urothelium of anuric patients on long-term hemodialysis, sampled at the time of renal transplantation, to investigate the expression of urothelial differentiation-associated antigens, including uroplakins (UPIa, UPIb, UPII, and UPIIIa), cytokeratin isotypes (CK7, CK8, CK13, CK14, CK17, CK18, and CK20), nuclear hormone receptors [peroxisome proliferators activated receptor-gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha)], and a cell cycle marker (Ki-67). To determine whether urinary metabolites of the arachidonic pathway could induce urothelial differentiation, cultured normal human urothelial (NHU) cells were treated with 15-deoxy-Delta 12, 14-prostaglandin J(2) (15d-PGJ(2)) and prostaglandin J(2) (PGJ(2)). The expression levels of the markers of differentiation, the uroplakins, were assessed by ribonuclease protection assay.Results. When compared in a blinded analysis against control normal urothelium, no significant changes were found in the expression or localization patterns of any of the antigens studied in the anuric patients. Furthermore, neither 15d-PGJ(2) nor PGJ(2) were able to induce expression of the UPII gene in NHU cells, in contrast to cultures exposed to the pharmacologic PPAR-gamma agonist, troglitazone.Conclusion. These data provide prima facie evidence that exogenous urine-derived factors do not modulate the differentiation program in urothelium, suggesting that other urothelial- or serum-derived factors are likely to be involved. These findings are important in understanding post-developmental maturation and functional relationships in urologic tissues of the adult organism.",

keywords = "urothelium, PPAR, differentiation, anuria, prostaglandin, bladder, PROLIFERATOR-ACTIVATED RECEPTOR, TRANSITIONAL-CELL CARCINOMA, UROPLAKIN GENE-EXPRESSION, PPAR-GAMMA, 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2), HETERODIMER FORMATION, MEMBRANE-PROTEINS, HUMAN TISSUES, IN-VITRO, LIGANDS",

author = "J Stahlschmidt and Varley, {C L} and G Toogood and Selby, {P J} and J Southgate",

year = "2005",

month = sep,

language = "English",

volume = "68",

pages = "1032--1040",

journal = "Kidney international",

issn = "0085-2538",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - Urothelial differentiation in chronically urine-deprived bladders of patients with end-stage renal disease

AU - Stahlschmidt, J

AU - Varley, C L

AU - Toogood, G

AU - Selby, P J

AU - Southgate, J

PY - 2005/9

Y1 - 2005/9

N2 - Background. It is unknown whether normal bladder voiding function, or soluble factors present in urine, contribute to the maturation and maintenance of the differentiated state of the uroepithelial cell lining of the lower urinary tract.Methods. We used the urothelium of anuric patients on long-term hemodialysis, sampled at the time of renal transplantation, to investigate the expression of urothelial differentiation-associated antigens, including uroplakins (UPIa, UPIb, UPII, and UPIIIa), cytokeratin isotypes (CK7, CK8, CK13, CK14, CK17, CK18, and CK20), nuclear hormone receptors [peroxisome proliferators activated receptor-gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha)], and a cell cycle marker (Ki-67). To determine whether urinary metabolites of the arachidonic pathway could induce urothelial differentiation, cultured normal human urothelial (NHU) cells were treated with 15-deoxy-Delta 12, 14-prostaglandin J(2) (15d-PGJ(2)) and prostaglandin J(2) (PGJ(2)). The expression levels of the markers of differentiation, the uroplakins, were assessed by ribonuclease protection assay.Results. When compared in a blinded analysis against control normal urothelium, no significant changes were found in the expression or localization patterns of any of the antigens studied in the anuric patients. Furthermore, neither 15d-PGJ(2) nor PGJ(2) were able to induce expression of the UPII gene in NHU cells, in contrast to cultures exposed to the pharmacologic PPAR-gamma agonist, troglitazone.Conclusion. These data provide prima facie evidence that exogenous urine-derived factors do not modulate the differentiation program in urothelium, suggesting that other urothelial- or serum-derived factors are likely to be involved. These findings are important in understanding post-developmental maturation and functional relationships in urologic tissues of the adult organism.

AB - Background. It is unknown whether normal bladder voiding function, or soluble factors present in urine, contribute to the maturation and maintenance of the differentiated state of the uroepithelial cell lining of the lower urinary tract.Methods. We used the urothelium of anuric patients on long-term hemodialysis, sampled at the time of renal transplantation, to investigate the expression of urothelial differentiation-associated antigens, including uroplakins (UPIa, UPIb, UPII, and UPIIIa), cytokeratin isotypes (CK7, CK8, CK13, CK14, CK17, CK18, and CK20), nuclear hormone receptors [peroxisome proliferators activated receptor-gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha)], and a cell cycle marker (Ki-67). To determine whether urinary metabolites of the arachidonic pathway could induce urothelial differentiation, cultured normal human urothelial (NHU) cells were treated with 15-deoxy-Delta 12, 14-prostaglandin J(2) (15d-PGJ(2)) and prostaglandin J(2) (PGJ(2)). The expression levels of the markers of differentiation, the uroplakins, were assessed by ribonuclease protection assay.Results. When compared in a blinded analysis against control normal urothelium, no significant changes were found in the expression or localization patterns of any of the antigens studied in the anuric patients. Furthermore, neither 15d-PGJ(2) nor PGJ(2) were able to induce expression of the UPII gene in NHU cells, in contrast to cultures exposed to the pharmacologic PPAR-gamma agonist, troglitazone.Conclusion. These data provide prima facie evidence that exogenous urine-derived factors do not modulate the differentiation program in urothelium, suggesting that other urothelial- or serum-derived factors are likely to be involved. These findings are important in understanding post-developmental maturation and functional relationships in urologic tissues of the adult organism.

KW - urothelium

KW - PPAR

KW - differentiation

KW - anuria

KW - prostaglandin

KW - bladder

KW - PROLIFERATOR-ACTIVATED RECEPTOR

KW - TRANSITIONAL-CELL CARCINOMA

KW - UROPLAKIN GENE-EXPRESSION

KW - PPAR-GAMMA

KW - 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2)

KW - HETERODIMER FORMATION

KW - MEMBRANE-PROTEINS

KW - HUMAN TISSUES

KW - IN-VITRO

KW - LIGANDS

M3 - Article

SN - 0085-2538

VL - 68

SP - 1032

EP - 1040

JO - Kidney international

JF - Kidney international

IS - 3

ER -