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You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP59)1 May 2024MP59-01 POLYSOMAL MRNA SEQUENCING REVEALS SATELLITE GLIAL SPECIFIC TRANSLATOME CHANGES IN ANIMAL MODELS OF CHRONIC PELVIC PAIN Sathish Kumar Yesupatham and Alison Xie Xiaoqiao Sathish Kumar YesupathamSathish Kumar Yesupatham and Alison Xie XiaoqiaoAlison Xie Xiaoqiao View All Author Informationhttps://doi.org/10.1097/01.JU.0001009476.18935.3b.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with bladder pain syndrome (BPS) experience chronic pelvic pain (CPP) and lower urinary tract symptoms (LUTS), such as urinary frequency, urgency, and nocturia. BPS symptoms are associated with nociceptive sensitization in the peripheral and central nervous system, which underlies visceral hyperalgesia. In our previous study, we reported that afferent hypersensitivity in bladder-projecting neurons plays a key role in the generation and maintenance of the symptom of CPP. Recent report using single nuclei sequencing and cell to cell communication (NeuronChat) reveals satellite glial cells communicate with all cell types including sensory neurons in dorsal root ganglia (DRGs). This study characterized satellite glial translatome in the sensory nervous system associated with CPP symptoms. METHODS: Satellite glial-specific inducible mice (Sox10-CreERT2) and ribosome-tagged mice (L10-eGFP) were bred to generate Sox10-TRAP animals used in this study. Visceral hypersensitivity was induced by intravesical instillations of the mouse recombinant vascular endothelial growth factor A (VEGFA). Sox10-TRAP mice were sacrificed after visceral hypersensitivity was confirmed by Von Frey assay and lumbosacral dorsal root ganglia (L1, L2, L6, S1 and S2) were dissected and homogenized to immunoprecipitate the actively transcribing ribosomes. RNA was isolated and TRAP-sequencing was performed. Samples were sequenced at a depth of 40 million reads per sample. Bioinformatics analysis was conducted using Partek® Flow® (Version 10.0) by Partek Inc. RESULTS: Intravesical instillations of VEGFA induced visceral mechanical hypersensitivity. Abdominal Von Frey assay showed visceral mechanical hypersensitivity in VEGFA-instilled mice when compared to saline-instilled animals. Satellite glial translatome (TRAP) was compared with total RNA (Input) transcriptome, DESEQ2 analysis revealed changes in nociceptor signaling. Gene set enrichment analysis revealed upregulation of notch signaling in satellite glial cells translatome during UCPPS. Potential therapeutic targets like Notch1, Serpine2, Ptprz1, Cxcr4, Ptn were also identified. CONCLUSIONS: Our data shows for the first time that satellite glial cells in peripheral sensory ganglia are actively involved in cell-to-cell communication during bladder pain. Further investigations including Ingenuity Pathway Analysis (IPA) will unveil the molecular mechanisms underlying VEGFA-induced bladder afferent hypersensitivity and shed lights on the etiology of BPS. Source of Funding: NIDDK 25B0965/5R01DK129260 (Xie) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e957 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Sathish Kumar Yesupatham More articles by this author Alison Xie Xiaoqiao More articles by this author Expand All Advertisement PDF downloadLoading ...
Yesupatham et al. (Mon,) studied this question.