Pd12-05 Immunological Significance of Newly Discovered Urothelial Collective Migration

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology (PD12)1 May 2024PD12-05 IMMUNOLOGICAL SIGNIFICANCE OF NEWLY DISCOVERED UROTHELIAL COLLECTIVE MIGRATION Takeshi Sano, Zhang Ning, Ryosuke Ikeuchi, Hideaki Takada, Kenji Nakamura, Toru Sakatani, Akihiro Hamada, Yuki Kita, Michiyuki Matsuda, and Takashi Kobayashi Takeshi SanoTakeshi Sano , Zhang NingZhang Ning , Ryosuke IkeuchiRyosuke Ikeuchi , Hideaki TakadaHideaki Takada , Kenji NakamuraKenji Nakamura , Toru SakataniToru Sakatani , Akihiro HamadaAkihiro Hamada , Yuki KitaYuki Kita , Michiyuki MatsudaMichiyuki Matsuda , and Takashi KobayashiTakashi Kobayashi View All Author Informationhttps://doi.org/10.1097/01.JU.0001008772.30001.48.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravital imaging of the mouse bladder identified a process of urothelial collective cell migration (uCCM) caused by intravesical administration of various immunogenic substances. This study aimed to investigate the mechanism and immunological significance of this newly discovered urothelial migration. METHODS: J96 (uropathogenic E. coli strain), lipopolysaccharide (LPS), and Bacillus Calmette-Guérin (BCG, Tokyo strain) were individually injected into the bladder of C57BL/6 mice expressing a cyan fluorescent protein in their cell nuclei. While mice were under general anesthesia induced by isoflurane, we used two-photon excitation microscopy, which enables deep tissue imaging, to visualize the urothelium. Dasatinib, a Src inhibitor, and PF-573228, a focal adhesion kinase (FAK) inhibitor, were individually administered intravenously or orally. TAK-242, a Toll-like receptor 4 (TLR4) inhibitor, was administered intravenously, followed by intravesical administration. To induce bladder infection, J96 was injected into the bladder and allowed to incubate for 30 minutes. Bladder extraction took place after six hours for the analysis of J96 infection. Trajectories and velocities of uCCM were analyzed using MetaMorph software. RESULTS: uCCM started 4 to 6 hours after intravesical injection of all the immunogenic substances, including J96, LPS, and BCG (Figure 1). The mean velocity of uCCM induced by these substances was 39.6 μm/h (range 34.3-45.2) while uCCM did not occur without treatment. Remarkably, both intravenous and oral administration of dasatinib and PF-573228 effectively delayed J96-induced uCCM. Intriguingly, the inhibition of uCCM through oral administration of dasatinib and PF-573228 significantly heightened J96 infection. Furthermore, TAK-242 treatment almost completely abrogated LPS-induced uCCM. CONCLUSIONS: uCCM induced by immunogenic substances appeared to depend on the integrin-FAK signaling pathway. Inhibition of this migration enhanced the infection caused by uropathogenic E. coli, suggesting that it may play an immunological role against bladder infection. This immunological function may be associated with the innate immune response, possibly mediated by pattern recognition receptors, such as TLR4. Thus, enhancement of this migration may be a novel strategy against various infectious diseases of the bladder. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e257 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Takeshi Sano More articles by this author Zhang Ning More articles by this author Ryosuke Ikeuchi More articles by this author Hideaki Takada More articles by this author Kenji Nakamura More articles by this author Toru Sakatani More articles by this author Akihiro Hamada More articles by this author Yuki Kita More articles by this author Michiyuki Matsuda More articles by this author Takashi Kobayashi More articles by this author Expand All Advertisement PDF downloadLoading ...