MP28-17 FOXA1 EXPRESSION IS REQUIRED FOR MAINTENANCE OF SUPERFICIAL UMBRELLA CELLS IN THE UROTHELIUM

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I (MP28)1 Apr 2020MP28-17 FOXA1 EXPRESSION IS REQUIRED FOR MAINTENANCE OF SUPERFICIAL UMBRELLA CELLS IN THE UROTHELIUM Lauren Shuman*, Jenna Buckwalter, Thomas Wildermuth, Klaus Kaestner, Cathy Mendelsohn, and David DeGraff Lauren Shuman*Lauren Shuman* More articles by this author , Jenna BuckwalterJenna Buckwalter More articles by this author , Thomas WildermuthThomas Wildermuth More articles by this author , Klaus KaestnerKlaus Kaestner More articles by this author , Cathy MendelsohnCathy Mendelsohn More articles by this author , and David DeGraffDavid DeGraff More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000867.017AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Chronic injury of the urothelium is associated with bladder pain syndrome and voiding dysfunction for which there are presently no cures. Therefore, understanding mechanisms responsible for the maintenance of urothelial differentiation and regeneration is important. Moreover, identifying molecular contributors to these processes could result in novel approaches to enhance healing. Forkhead Box A1 (Foxa1) is a transcription factor important for the regulation of tissue-specific gene expression in the urothelium and other cell types. We previously reported that inducible Foxa1 knockout (KO) in adult mice results in hyperplasia, squamous differentiation, and reduced expression of tissue-specific genes in the urothelium. Here, we use a Upk2Cre driven KO of Foxa1 to determine the impact of early Foxa1 inactivation in urothelial development and differentiation. METHODS: The Upk2Cre mouse line (expressed at embryonic day 13) was bred with previously described Foxa1loxp/loxp mice. Control and Upk2Cre/Foxa1loxp/loxp mice were sacrificed at 3 months of age and bladders were analyzed using hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and immunofluorescence (IF). RESULTS: While urothelium from control mice exhibited a normal number of superficial umbrella, intermediate, and basal urothelial cells, the number of umbrella cells within the bladders of a subset of Upk2Cre/Foxa1loxp/loxp mice was significantly reduced in number (p=0.003; Student’s t-test), with IHC confirming KO in remaining superficial urothelial cells. The urothelium of Foxa1 KO mice also often appeared dysmorphic and umbrella cells were undetectable in a subset of bladders. In addition, while IF confirmed decreases in the number of Upk3+/Krt20+/Tp63- superficial urothelial cells, we also show that Foxa1 KO bladders have a reduced number of Upk3+/Tp63+ intermediate cells. CONCLUSIONS: These results suggest Foxa1 expression is required for normal urothelial development and/or maintenance of superficial and intermediate urothelial populations. However, it is still unknown if Foxa1 expression plays a role in the maintenance of basal urothelium, or if Foxa1 is required for urothelial regeneration following injury. Therefore, future studies will focus on these and other areas of importance. Source of Funding: 5U54DK104309 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e426-e426 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lauren Shuman* More articles by this author Jenna Buckwalter More articles by this author Thomas Wildermuth More articles by this author Klaus Kaestner More articles by this author Cathy Mendelsohn More articles by this author David DeGraff More articles by this author Expand All Advertisement PDF downloadLoading ...