2121 GENOME WIDE ANALYSIS OF DIFFERENTIALLY EXPRESSED GENES IN THE KIDNEYS OF A RAT NEPHROLITHIASIS MODEL (2012)

You have accessJournal of UrologyStone Disease: Evaluation & Medical Management I1 Apr 20122121 GENOME WIDE ANALYSIS OF DIFFERENTIALLY EXPRESSED GENES IN THE KIDNEYS OF A RAT NEPHROLITHIASIS MODEL Sunil Joshi, Benjamin Saylor, Wei Wang, Ammon Peck, and Saeed Khan Sunil JoshiSunil Joshi Gainesville, FL More articles by this author , Benjamin SaylorBenjamin Saylor Gainesville, FL More articles by this author , Wei WangWei Wang Gainesville, FL More articles by this author , Ammon PeckAmmon Peck Gainesville, FL More articles by this author , and Saeed KhanSaeed Khan Gainesville, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2290AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have proposed that production of reactive oxygen species (ROS) is an important contributor to renal injury and inflammation following exposure to oxalate or calcium-oxalate crystals. The present study was conducted to determine, utilizing global transcriptome analyses, if the NADPH oxidase system is activated in kidneys of rats fed a diet leading to hyperoxaluria and crystal deposition. METHODS Age-, sex- and weight-matched rats were divided into 2 groups (n=6/group). One group was fed a regular rat chow diet, while the second group received regular rat chow supplemented with 5% w/w hydroxyl-L-proline (HLP). After 28 days, each rat was euthanized, their kidneys freshly explanted and dissected to obtain both cortex and medulla tissues. Total RNA was extracted from each tissue and subjected to genomic microarrays to obtain transcriptome data. KEGG was used to identify gene clusters. Immunohistochemistry confirmed protein expressions of selected genes. RESULTS Genes encoding both membrane- and cytosolic-NADPH oxidase complex-associated proteins, together with Rac1 and Rac2, were coordinately and significantly up-regulated in both renal medulla and cortex tissue in the HLP-fed rats compared to controls. Activation of NADPH oxidase appears to occur via the angiotensin-II/angiotensin-II receptor-2 pathway, although the DAG-PKC pathway of neutrophils may also contribute. Interestingly, renal tissues from rats presenting with hyperoxaluria with or without crystal deposition exhibited multiple differentially-expressed gene sets. Immunohistochemical staining confirmed these up-regulated gene expressions. Simultaneously, genes encoding ROS scavenger proteins (e.g. SOD and catalase) were down-regulated. Treatment of rats fed HLP with Apocynin showed a complete reversal of ROS associated gene expression. CONCLUSIONS A strong up-regulation of oxidative/respiratory burst involving the NADPH oxidase system, activated via the angiotensin-II and DAG-PKC pathways, occurs in kidneys of hyperoxaluric rats,reversible by Apocynin treatment. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e856-e857 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sunil Joshi Gainesville, FL More articles by this author Benjamin Saylor Gainesville, FL More articles by this author Wei Wang Gainesville, FL More articles by this author Ammon Peck Gainesville, FL More articles by this author Saeed Khan Gainesville, FL More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...