title: Impact of diabetes mellitus on bladder uroepithelial cells.
abstract: Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in female Sprague-Dawley rats compared with age-matched control tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible breach in barrier function. One causative factor may be metabolic burden due to chronic hyperglycemia, suggested by upregulation of the polyol pathway and glucose transport genes in DM UT. While superficial UT repopulation occurred by 20 wk DM, the phenotype was different, with significant upregulation of receptors associated with UT mechanosensation (transient receptor potential vanilloid subfamily member 1; TRPV1) and UT autocrine/paracrine signaling (acetylcholine receptors AChR-M2 and -M3, purinergic receptors P2X(2) and P2X(3)). Compromised barrier function and alterations in UT mechanosensitivity and cell signaling could contribute to bladder instability, hyperactivity, and altered bladder sensation by modulating activity of afferent nerve endings, which appose the urothelium. Our results show that DM impacts urothelial homeostasis and may contribute to the underlying mechanisms of DBD.
authors.affiliation: Univ. of Pittsburgh, Dept. of Medicine, Pittsburgh, PA 15213, USA. ahannam@pitt.edu
authors.forename: Ann T
authors.initials: AT
authors.lastname: Hanna-Mitchell
authors.forename: Giovanni W
authors.initials: GW
authors.lastname: Ruiz
authors.forename: Firouz
authors.initials: F
authors.lastname: Daneshgari
authors.forename: Guiming
authors.initials: G
authors.lastname: Liu
authors.forename: Gerard
authors.initials: G
authors.lastname: Apodaca
authors.forename: Lori A
authors.initials: LA
authors.lastname: Birder
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019898:Autocrine Communication / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D048909:Diabetes Complications / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D040542:Mechanotransduction, Cellular / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D019899:Paracrine Communication / Q000235:genetics; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism / Q000648:ultrastructure*; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D001786:Blood Glucose