MP41-01 EXTRACELLULAR VESICLES REGULATE GLOMERULAR VEGF HOMEOSTASIS IN CHRONIC KIDNEY DISEASE

Abstract

You have accessJournal of UrologyStem Cell Research1 Apr 2017MP41-01 EXTRACELLULAR VESICLES REGULATE GLOMERULAR VEGF HOMEOSTASIS IN CHRONIC KIDNEY DISEASE Sargis Sedrakyan, Valentina Villani, Stefano Porta, Stefano Da Sacco, Nikita Tripuraneni, Andrea Achena, Maria Lavarreda-Pearce, Hasmik Soloyan, Roger De Filippo, Benedetta Bussolati, and Laura Perin Sargis SedrakyanSargis Sedrakyan More articles by this author , Valentina VillaniValentina Villani More articles by this author , Stefano PortaStefano Porta More articles by this author , Stefano Da SaccoStefano Da Sacco More articles by this author , Nikita TripuraneniNikita Tripuraneni More articles by this author , Andrea AchenaAndrea Achena More articles by this author , Maria Lavarreda-PearceMaria Lavarreda-Pearce More articles by this author , Hasmik SoloyanHasmik Soloyan More articles by this author , Roger De FilippoRoger De Filippo More articles by this author , Benedetta BussolatiBenedetta Bussolati More articles by this author , and Laura PerinLaura Perin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1269AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tight regulation of paracrine VEGF signaling between podocytes and glomerular endothelial cells (GEC) is required for maintenance of the glomerular filtration barrier (GFB) structure and function. Disruption of VEGF homeostasis has been implicated in various types of glomerular diseases. However, current therapies neither specifically target the glomerulus nor the VEGF pathway but in addition present multiple side effects. Therefore, identification of new approaches aimed at restoring local VEGF remains a potential therapeutic target to treat glomerular disease. We previously showed that amniotic fluid stem cells (AFSC) are renoprotective in Alport Syndrome (AS), a model of CKD. They home within the diseased glomeruli and secrete extracellular vesicles (EVs). EVs play key role in stem cell mediated paracrine function, including the kidney. Herein, we demonstrate that AFSC derived EVs regulate VEGF/VEGFRs signaling balance in AS GEC via modulation of sFlt1, the soluble isoform of VEGFR1. METHODS We measured VEGF activity in AS glomeruli by WB. We assessed VEGF/VEGF-Rs activity in GEC, including the sFlt1. We characterized AFSC-EVs cargo by FACS and by miRs arrays and evaluated their potential to affect VEGF biology in GEC. RESULTS Glomeruli from AS mice showed increased VEGF activity through increased phosphorylation of VEGFR-2 early on during progression accompanied by modulation of sFlt1. These observations were associated with GEC damage that showed altered VEGFR signaling. Importantly, EVs presented with VEGFRs and angiomodulatory microRNA. These EVs successfully integrated within GEC and modulated VEGF activity. EVs lacking both the full and soluble VEGFR-1 failed to rescue GEC from VEGF inflicted damage. CONCLUSIONS In conclusion, we demonstrated for the first time the aberration of VEGF signaling within AS glomeruli. We further showed that AFSC derived EVs play important role in maintaining glomerular homeostasis of VEGF signaling, presenting with a potential for new targeted therapies in CKD. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e531-e532 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Sargis Sedrakyan More articles by this author Valentina Villani More articles by this author Stefano Porta More articles by this author Stefano Da Sacco More articles by this author Nikita Tripuraneni More articles by this author Andrea Achena More articles by this author Maria Lavarreda-Pearce More articles by this author Hasmik Soloyan More articles by this author Roger De Filippo More articles by this author Benedetta Bussolati More articles by this author Laura Perin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...