title: Evidence for bladder urothelial pathophysiology in functional bladder disorders.
abstract: Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.
authors.affiliation: Division of Infectious Diseases, University of Maryland School of Medicine and the VA Maryland Health Care System, 10 North Greene Street, Room 3B-184, Baltimore, MD 21201, USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Keay
authors.affiliation: Departments of Medicine and Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, A 1217 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Birder
authors.affiliation: Department of Urology, Yale School of Medicine, 789 Howard Avenue, FMP 309, P.O. Box 208058, New Haven, CT 06519-8058, USA.
authors.forename: Toby C
authors.initials: TC
authors.lastname: Chai
mesh_terms: D000818:Animals; D006801:Humans; D001743:Urinary Bladder / Q000473:pathology*; D001745:Urinary Bladder Diseases / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*