Cell Biology and Physiology of the Uroepithelium

Overview

Journal Am J Physiol Renal Physiol

Publisher American Physiological Society

Specialties Nephrology
Physiology

Date 2009 Jul 10

PMID 19587142

Citations 174

Authors

Puneet Khandelwal

Soman N Abraham

Gerard Apodaca

Affiliations

Soon will be listed here.

Abstract

The uroepithelium sits at the interface between the urinary space and underlying tissues, where it forms a high-resistance barrier to ion, solute, and water flux, as well as pathogens. However, the uroepithelium is not simply a passive barrier; it can modulate the composition of the urine, and it functions as an integral part of a sensory web in which it receives, amplifies, and transmits information about its external milieu to the underlying nervous and muscular systems. This review examines our understanding of uroepithelial regeneration and how specializations of the outermost umbrella cell layer, including tight junctions, surface uroplakins, and dynamic apical membrane exocytosis/endocytosis, contribute to barrier function and how they are co-opted by uropathogenic bacteria to infect the uroepithelium. Furthermore, we discuss the presence and possible functions of aquaporins, urea transporters, and multiple ion channels in the uroepithelium. Finally, we describe potential mechanisms by which the uroepithelium can transmit information about the urinary space to the other tissues in the bladder proper.

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References

Min G, Stolz M, Zhou G, Liang F, Sebbel P, Stoffler D . Localization of uroplakin Ia, the urothelial receptor for bacterial adhesin FimH, on the six inner domains of the 16 nm urothelial plaque particle. J Mol Biol. 2002; 317(5):697-706. DOI: 10.1006/jmbi.2002.5442. View

Lewis S, de Moura J . Incorporation of cytoplasmic vesicles into apical membrane of mammalian urinary bladder epithelium. Nature. 1982; 297(5868):685-8. DOI: 10.1038/297685a0. View

Sakakibara K, Sato K, Yoshino K, Oshiro N, Hirahara S, Hasan A . Molecular identification and characterization of Xenopus egg uroplakin III, an egg raft-associated transmembrane protein that is tyrosine-phosphorylated upon fertilization. J Biol Chem. 2005; 280(15):15029-37. DOI: 10.1074/jbc.M410538200. View

Casanova J, Wang X, Kumar R, Bhartur S, Navarre J, Woodrum J . Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Mol Biol Cell. 1999; 10(1):47-61. PMC: 25153. DOI: 10.1091/mbc.10.1.47. View

Kanai A, Epperly M, Pearce L, Birder L, Zeidel M, Meyers S . Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol. 2003; 286(1):H13-21. DOI: 10.1152/ajpheart.00737.2003. View

Wang H, Liang F, Kong X . Characteristics of the phagocytic cup induced by uropathogenic Escherichia coli. J Histochem Cytochem. 2008; 56(6):597-604. PMC: 2386762. DOI: 10.1369/jhc.2008.950923. View

Kreft M, Sterle M, Veranic P, Jezernik K . Urothelial injuries and the early wound healing response: tight junctions and urothelial cytodifferentiation. Histochem Cell Biol. 2005; 123(4-5):529-39. DOI: 10.1007/s00418-005-0770-9. View

Mayor S, Pagano R . Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol. 2007; 8(8):603-12. PMC: 7617177. DOI: 10.1038/nrm2216. View

Acharya P, Beckel J, Ruiz W, Wang E, Rojas R, Birder L . Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium. Am J Physiol Renal Physiol. 2004; 287(2):F305-18. DOI: 10.1152/ajprenal.00341.2003. View

10.

Shafik A, Shafik I, El Sibai O, Shafik A . Changes in the urine composition during its passage through the ureter. A concept of urothelial function. Urol Res. 2005; 33(6):426-8. DOI: 10.1007/s00240-005-0499-x. View

11.

Lapierre L, Kumar R, Hales C, Navarre J, Bhartur S, Burnette J . Myosin vb is associated with plasma membrane recycling systems. Mol Biol Cell. 2001; 12(6):1843-57. PMC: 37346. DOI: 10.1091/mbc.12.6.1843. View

12.

Fowler C, Jewkes D, McDonald W, Lynn B, de Groat W . Intravesical capsaicin for neurogenic bladder dysfunction. Lancet. 1992; 339(8803):1239. DOI: 10.1016/0140-6736(92)91186-c. View

13.

Southgate J, Kennedy W, Hutton K, Trejdosiewicz L . Expression and in vitro regulation of integrins by normal human urothelial cells. Cell Adhes Commun. 1995; 3(3):231-42. DOI: 10.3109/15419069509081289. View

14.

Wu X, Lin J, Walz T, Haner M, Yu J, Aebi U . Mammalian uroplakins. A group of highly conserved urothelial differentiation-related membrane proteins. J Biol Chem. 1994; 269(18):13716-24. View

15.

Ibraghimov-Beskrovnaya O, Dackowski W, Foggensteiner L, Coleman N, Thiru S, Petry L . Polycystin: in vitro synthesis, in vivo tissue expression, and subcellular localization identifies a large membrane-associated protein. Proc Natl Acad Sci U S A. 1997; 94(12):6397-402. PMC: 21061. DOI: 10.1073/pnas.94.12.6397. View

16.

Varley C, Garthwaite M, Cross W, Hinley J, Trejdosiewicz L, Southgate J . PPARgamma-regulated tight junction development during human urothelial cytodifferentiation. J Cell Physiol. 2006; 208(2):407-17. PMC: 1522040. DOI: 10.1002/jcp.20676. View

17.

Mysorekar I, Mulvey M, Hultgren S, Gordon J . Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli. J Biol Chem. 2001; 277(9):7412-9. DOI: 10.1074/jbc.M110560200. View

18.

Aboushwareb T, Zhou G, Deng F, Turner C, Andersson K, Tar M . Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice. Neurourol Urodyn. 2009; 28(8):1028-33. PMC: 4048927. DOI: 10.1002/nau.20688. View

19.

Yu W, Khandelwal P, Apodaca G . Distinct apical and basolateral membrane requirements for stretch-induced membrane traffic at the apical surface of bladder umbrella cells. Mol Biol Cell. 2008; 20(1):282-95. PMC: 2613117. DOI: 10.1091/mbc.e08-04-0439. View

20.

Payne C, Mosbaugh P, Forrest J, Evans R, Whitmore K, Antoci J . Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol. 2005; 173(5):1590-4. DOI: 10.1097/01.ju.0000154631.92150.ef. View