MP48-05 MULTIOMICS-BASED CHARACTERIZATION OF BLADDER REMODELING AFTER SPINAL CORD INJURY

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (MP48)1 Apr 2020MP48-05 MULTIOMICS-BASED CHARACTERIZATION OF BLADDER REMODELING AFTER SPINAL CORD INJURY Ali Hashemi Gheinani*, Bryan S. Sack, Mary Piper, Hussein Atta, Justin F. Cotellessa, George Lambrinos, Kyle Costa, Claire Doyle, Susan Patalano, Vivian Cristofaro, Maryrose Sullivan, Jill A Macoska, and Rosalyn Adam Ali Hashemi Gheinani*Ali Hashemi Gheinani* More articles by this author , Bryan S. SackBryan S. Sack More articles by this author , Mary PiperMary Piper More articles by this author , Hussein AttaHussein Atta More articles by this author , Justin F. CotellessaJustin F. Cotellessa More articles by this author , George LambrinosGeorge Lambrinos More articles by this author , Kyle CostaKyle Costa More articles by this author , Claire DoyleClaire Doyle More articles by this author , Susan PatalanoSusan Patalano More articles by this author , Vivian CristofaroVivian Cristofaro More articles by this author , Maryrose SullivanMaryrose Sullivan More articles by this author , Jill A MacoskaJill A Macoska More articles by this author , and Rosalyn AdamRosalyn Adam More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000903.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Suprasacral spinal cord injury (SCI) is associated with profound remodeling of the bladder wall and with the development of neurogenic detrusor overactivity (NDO). However, the molecular pathways driving remodeling and how these contribute to functional alterations remain incompletely defined. The objective of this study was to use multi-omics approach to assess time-dependent transcriptional changes following SCI and to identify signaling pathways contributing to bladder wall remodeling and fibrosis. METHODS: Complete spinal cord transection at T8 was performed in male Sprague Dawley rats, with bladders harvested at 2, 8, and 16 weeks after injury. Age-matched, non-injured rats served as controls. Urine and blood were collected prior to sacrifice. RNA sequencing, small RNA sequencing, proteomics, phosphoproteomics was performed on full thickness bladder from rats from all time points. Urinary proteomics was also performed. Tissues were analysed by H&E staining as well as Masson’s trichrome staining (MTS) to assess the extent of fibrosis. RESULTS: Evaluation of bladder-to-body weight ratio revealed significant remodeling in bladders from SCI versus control rats. Quantification of MTS-stained slides showed a significant increase in collagen deposition in SCI versus controls at each time point. The intensity of changes reflected in biological functions showed an increase from 2 to 8 weeks but this increase was less enhanced from 8 to 16 weeks. Proteomics analysis indicated differential phosphorylation of actin cytoskeleton signaling, ILK signaling, RhoA signaling and Rho family GTPases signaling pathways in SCI compared to controls. The correlation between transcript levels and protein abundance was 25%. CONCLUSIONS: Our integrated, multi-omics analysis revealed perturbations in a variety of physiologically relevant pathways including those associated with innervation and cytoskeletal remodeling. These findings are consistent with the profound changes in bladder wall morphology following SCI. Integration of multiple omics datasets reveals novel insights into the pathogenesis of neurogenic bladder and implicates druggable kinases as regulators of pathologic remodeling. Source of Funding: R01 DK077195 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e696-e696 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ali Hashemi Gheinani* More articles by this author Bryan S. Sack More articles by this author Mary Piper More articles by this author Hussein Atta More articles by this author Justin F. Cotellessa More articles by this author George Lambrinos More articles by this author Kyle Costa More articles by this author Claire Doyle More articles by this author Susan Patalano More articles by this author Vivian Cristofaro More articles by this author Maryrose Sullivan More articles by this author Jill A Macoska More articles by this author Rosalyn Adam More articles by this author Expand All Advertisement PDF downloadLoading ...