MP58-01 DISCOVERY OF RANDALL’S PLAQUE GENE EXPRESSION PROFILING IN CALCIUM OXALATE STONE FORMERS BY IMMUNOHISTOCHEMICAL GENOME-WIDE ANALYSIS

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2016MP58-01 DISCOVERY OF RANDALL’S PLAQUE GENE EXPRESSION PROFILING IN CALCIUM OXALATE STONE FORMERS BY IMMUNOHISTOCHEMICAL GENOME-WIDE ANALYSIS Kazumi Taguchi, Shuzo Hamamoto, Atsushi Okada, Rei Unno, Hideyuki Kamisawa, Taku Naiki, Ryosuke Ando, Keiichi Tozawa, Kenjiro Kohri, and Takahiro Yasui Kazumi TaguchiKazumi Taguchi More articles by this author , Shuzo HamamotoShuzo Hamamoto More articles by this author , Atsushi OkadaAtsushi Okada More articles by this author , Rei UnnoRei Unno More articles by this author , Hideyuki KamisawaHideyuki Kamisawa More articles by this author , Taku NaikiTaku Naiki More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Keiichi TozawaKeiichi Tozawa More articles by this author , Kenjiro KohriKenjiro Kohri More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.799AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Randall's plaque (RP) is the origin of renal calcification on which idiopathic calcium oxalate (CaOx) kidney stones develop; however, its exact role in CaOx crystal formation remains unknown. We previously reported the potential therapeutic roles of osteopontin and macrophage (Mϕ) for CaOx kidney stone formation using transgenic mouse and genome-wide analysis. To establish the genomic pathogenesis of RP, we performed a microarray as well as immunohistochemical analysis for comparing the gene expressions among renal papillary RP and normal tissue of 23 CaOx, six calcium phosphate (CaP) stone formers, and normal papillary tissue of seven control patients. METHODS We obtained the papillary tissue samples by cold cup biopsy during retrograde intrarenal surgery or ureteroscopy. Comparisons were made between: 1) RP of CaOx and CaP stone formers; 2) RP and normal tissue of CaOx stone formers and normal tissue of control patients; and 3) between RP and normal tissue of CaOx stone formers. The analyses were performed using GeneSpring13.1® and IPA® software. We then validated the results using reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS Genes that expressed more than two-fold higher levels in CaP than in CaOx stone formers included fibrinogen, collagens, P38 mitogen-activated protein kinase (MAPK), nuclear factor κB, and chemokines but decreased expressions of immune-related molecules, such as immunoglobulin, interferon-α, and T-cell receptor. Papillary tissue both from RP and normal lesions of CaOx stone-forming patients expressed activated cellular hyperpolarization, reproductive development, and molecular transport. Compared to normal papillary tissue, RP tissue contained upregulated lipocalin 2, interleukin 11, prostaglandin-endoperoxide synthase 1, glutathione peroxidase 3, and monocyte to Mϕ differentiation but downregulation of solute carrier family 12 member 1 and sodium leak channel non-selective (either > 2.0- or 0.5-fold, p < 0.01). Network and toxicity analyses showed that these genes were associated with activated MAPK, the Akt/phosphatidylinositol 3-kinase pathway, and pro-inflammatory cytokines, which caused renal injury and oxidative stress. CONCLUSIONS Our results are the first to establish that genes related to renal dysfunction, pro-inflammation, oxidative stress, and ion transport induce the development of RP in CaOx stone formers. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e775 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kazumi Taguchi More articles by this author Shuzo Hamamoto More articles by this author Atsushi Okada More articles by this author Rei Unno More articles by this author Hideyuki Kamisawa More articles by this author Taku Naiki More articles by this author Ryosuke Ando More articles by this author Keiichi Tozawa More articles by this author Kenjiro Kohri More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...