title: Correlation between urothelial differentiation and sensory proteins P2X3, P2X5, TRPV1, and TRPV4 in normal urothelium and papillary carcinoma of human bladder.
abstract: Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.
authors.affiliation: Department of Urology, University Medical Centre Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia.
authors.forename: Igor
authors.initials: I
authors.lastname: Sterle
authors.affiliation: Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Daša
authors.initials: D
authors.lastname: Zupančič
authors.affiliation: Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Romih
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000378:metabolism*; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D058485:Receptors, Purinergic P2X5 / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000166:cytology*
chemical_list: D058477:Receptors, Purinergic P2X3; D058485:Receptors, Purinergic P2X5; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C416986:TRPV4 protein, human