MP24-09 REG3γ STRATIFIES THE BLADDER UROTHELIUM WITH SUBVERSION OF THIS PATHWAY BY UPEC DURING CHRONIC CYSTITIS
Year: 2016
Type: article
Abstract: You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2016MP24-09 REG3γ STRATIFIES THE BLADDER UROTHELIUM WITH SUBVERSION OF THIS PATHWAY BY UPEC DURING CHRONIC CYSTITIS Christina Ching, Ashley Jackson, Birong Li, Keith Pierce, David Hains, Kirk McHugh, and Brian Becknell Christina ChingChristina Ching More articles by this author , Ashley JacksonAshley Jackson More articles by this author , Birong LiBirong Li More articles by this author , Keith PierceKeith Pierce More articles by this author , David HainsDavid Hains More articles by this author , Kirk McHughKirk McHugh More articles by this author , and Brian BecknellBrian Becknell More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.765AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Reg3γ is an antimicrobial peptide whose physiologic function in vivo is unknown. We previously demonstrated urothelial production of Reg3γ peptide during Gram-negative cystitis despite absent antimicrobial activity toward uropathogenic Escherichia coli (UPEC) suggesting alternative functions for Reg3γ in the urinary tract. We tested the consequence of Reg3γ deletion on urothelial structure and susceptibility to UPEC infection. METHODS We measured Reg3γ mRNA expression during bladder ontogeny by quantitative RT-PCR and localized the Reg3γ transcript by in situ hybridization in C57BL/6J mice. We evaluated urothelial markers in Reg3γ knockout (Reg3γ-/-) and control bladders by immunofluorescence. We enumerated urothelial cells and measured bladder thickness in H&E sections using image software. We imaged adult Reg3γ-/- and control urinary tracts by terminal cystogram and ultrasound and challenged them with intravesical UPEC (10^7 colony forming units) to evaluate impact on urinary tract bacterial burden. RESULTS Bladder Reg3γ mRNA levels increase 3-fold at E14 (p<0.05) and localize to urothelial basal and intermediate layers by in situ hybridization. Similar results were obtained at E15 when there was first observed Keratin 20 expression suggesting terminal differentiation of superficial cells. Adult Reg3γ-/- bladders possess fewer total urothelial cells (p=0.015) and exhibit urothelial thinning (p=0.036). Immunofluorescence with Keratin 5 and Upk3a antibodies reveals absence of intermediate cells. A portion of adult Reg3γ-/- mice also demonstrate hydronephrosis (12%) and VUR (16%). Reg3γ protein localizes to intermediate cell layers during UPEC infection. While there was no initial difference in bacterial burden between Reg3γ-/- and control mice 6, 24, 48, or 72 hours post infection, urine and urinary tract bacterial recovery was significantly reduced in Reg3γ-/- mice 7 and 14 days post infection (p<0.05). CONCLUSIONS Reg3γ mRNA and protein expression occurs during stratification of bladder epithelium prior to terminal urothelial differentiation. Reg3γ deficiency causes urothelial thinning due to an absent intermediate cell layer with associated VUR and hydronephrosis. While UPEC infection induces Reg3γ expression, Reg3γ-/- mice clear UPEC infection more rapidly than controls suggesting UPEC induced Reg3γ expression promotes the persistence of urothelial reservoirs during chronic infection. Reg3γ could act as a novel therapeutic target in patients with chronic UTI. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e273 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Christina Ching More articles by this author Ashley Jackson More articles by this author Birong Li More articles by this author Keith Pierce More articles by this author David Hains More articles by this author Kirk McHugh More articles by this author Brian Becknell More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Authors: Christina Ching, Ashley Jackson, Birong Li, Keith Pierce, David Hains, Kirk McHugh, Brian Becknell
Institution: National Institutes of Health
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2328787076