2072 ROLE OF MATRIX GLA PROTEIN (MGP) IN STONE FORMATION, RESULTS OF EXPERIMENTAL STUDIES

Abstract

You have accessJournal of UrologyStone Disease: Basic Research (I)1 Apr 20132072 ROLE OF MATRIX GLA PROTEIN (MGP) IN STONE FORMATION, RESULTS OF EXPERIMENTAL STUDIES Aslam Khan, Wei Wang, and Saeed Khan Aslam KhanAslam Khan Gainesville, FL More articles by this author , Wei WangWei Wang 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.2013.02.2491AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Polymorphism of gene for matrix gla protein (MGP), a well known inhibitor of the deposition of apatite in arterial wall, is associated with both arterial calcification and myocardial infarct as well as kidney stone formation. Idiopathic kidney stones develop an apatitic Randall's plaques. Experimental investigations of MGP role in stone pathogenesis are limited. This study was performed to determine the effect of renal epithelial exposure to oxalate (Ox), calcium oxalate (CaOx) monohydrate (COM) or hydroxyapatite (HAP) crystal on the expression of MGP in vitro in cell culture as well as of Ox and CaOx crystals in a rat model of hyperoxaluria. METHODS MDCK cells in culture were exposed to 0.3, 0.5 or 1 mM Ox, 33, 66 or 133-150 ìg/cm2 of COM/HA for 3 to 72 hours. MGP expression and production by MDCK cells in culture was determined by western blotting and densitometric analysis. Enzyme linked immunosorbent assay (ELISA) was performed to determine the release of MGP into the medium. Hyperoxaluria was induced in male Sprague Dawley rats by feeding hydroxyl-L-proline (HLP) for 4 weeks. Immunohistochemistry was performed to detect renal MGP expression in response to hyperoxauria and CaOx crystal deposition. RESULTS Exposure to Ox, COM or HA crystals lead to the time and concentration dependent increase in the expression of MGP in the MDCK cells. Cellular response was quicker to COM and HA crystal exposure than the exposure to Ox. MGP expression was significantly higher after only 3 hours to COM or HA crystals while it took more than 6 hours when cells were exposed to Ox. MGP expression was increased in kidneys of the hyperoxaluric rats particularly in the renal peritubular vessels. CONCLUSIONS We confirm results of the earlier studies showing increased expression of MGP in renal tubular epithelial cells exposed to Ox or CaOx crystals. In addition we show that HA crystals also induce MGP expression. Most significant finding of this study is increased staining seen in renal preritubular vessels of the hyperoxaluric rats indicating that renal endothelial cells are involved in the synthesis of MGP. We propose that production of MGP is a normal response to lithogenic challenge. Mutation in MGP gene results in the production of a defective protein which is unable to inhibit crystallization and formation of Randall's plaques. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e850 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aslam Khan Gainesville, FL More articles by this author Wei Wang Gainesville, FL More articles by this author Saeed Khan Gainesville, FL More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...