722 IDENTIFICATION OF EPIGENETIC CHANGES IN CHRONIC BLADDER INFLAMMATION

Abstract

You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2012722 IDENTIFICATION OF EPIGENETIC CHANGES IN CHRONIC BLADDER INFLAMMATION In-Seon Choi, Kevin Yu, Erika De Guzman, Dan Weisenberger, Kyung Hwa Lee, Peter Laird, Peter Jones, David Warburton, Gangning Liang, and Chester Koh In-Seon ChoiIn-Seon Choi Los Angeles, CA More articles by this author , Kevin YuKevin Yu Los Angeles, CA More articles by this author , Erika De GuzmanErika De Guzman Los Angeles, CA More articles by this author , Dan WeisenbergerDan Weisenberger Los Angeles, CA More articles by this author , Kyung Hwa LeeKyung Hwa Lee Los Angeles, CA More articles by this author , Peter LairdPeter Laird Los Angeles, CA More articles by this author , Peter JonesPeter Jones Los Angeles, CA More articles by this author , David WarburtonDavid Warburton Los Angeles, CA More articles by this author , Gangning LiangGangning Liang Los Angeles, CA More articles by this author , and Chester KohChester Koh Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.807AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epigenetics plays an important role in the regulation of inflammatory genes in chronic diseases such as asthma and chronic obstructive pulmonary disease (COPD). However, epigenetic changes during non-cancer chronic bladder inflammation in children and adults have not been described previously. The purpose of this study was to determine whether epigenetic (DNA methylation) changes occur during chronic bladder inflammation. METHODS After animal care committee approval, chronic cystitis was induced in three groups of C57/BL6 mice using multiple weight-based intraperitoneal cyclophosphamide (CYP) injections over a period of 3 months. Retrieved bladders at multiple time points were analyzed using histology and immunohistochemistry to assess the severity of inflammation in comparison to untreated control mice. MethyLight assay was performed on bladder inflammation specimens to monitor epigenetic (DNA methylation) changes in comparison to control specimens. RESULTS H & E staining showed extensive edema and urothelial sloughing at 1 month of CYP injections, moderate edema at the 2-month time point, and resolution of the edema at the 3-month time point. PCNA staining revealed increased cell proliferation in the epithelial layer at the 1-month time point, but not at the 2- or 3-month time points. MethyLight assay revealed significant DNA methylation changes associated with the Calca, Line-1, Timp3, Igf2r and Mmp2 genes in the chronic bladder injury model (Figure 1). Maximum changes in DNA methylation were noted at the 1-month time point for all 5 genes, with hypomethylation for the Calca and Line-1 genes and hypomethylation for the Timp3, Igf2r, and Mmp2 genes in comparison to control tissue. CONCLUSIONS Maximum epigenetic changes associated with chronic bladder inflammation were noted at the 1-month time point, which correlated with histopathological changes. DNA methylation changes were noted in 5 cancer-related genes, Calca, Line-1, Timp3, Igf2r, and Mmp2, in this non-cancer chronic bladder inflammation model. Further experiments will help to elucidate the pathways associated with these genes during chronic bladder inflammation, and may lead to novel diagnostic and therapeutic advances. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e296-e297 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information In-Seon Choi Los Angeles, CA More articles by this author Kevin Yu Los Angeles, CA More articles by this author Erika De Guzman Los Angeles, CA More articles by this author Dan Weisenberger Los Angeles, CA More articles by this author Kyung Hwa Lee Los Angeles, CA More articles by this author Peter Laird Los Angeles, CA More articles by this author Peter Jones Los Angeles, CA More articles by this author David Warburton Los Angeles, CA More articles by this author Gangning Liang Los Angeles, CA More articles by this author Chester Koh Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...