MP07-03 THE PROTECTIVE ROLE OF ESTROGEN RECEPTOR Β IN RENAL CALCIUM OXALATE FORMATION VIA REDUCING THE LIVER OXALATE BIOSYNTHESIS AND RENAL CELL INJURY

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-03 THE PROTECTIVE ROLE OF ESTROGEN RECEPTOR Β IN RENAL CALCIUM OXALATE FORMATION VIA REDUCING THE LIVER OXALATE BIOSYNTHESIS AND RENAL CELL INJURY Wei Zhu, Wenbiao Ren, Chawnshang Chang, Edward M. Messing, Jean V. Joseph, Rajat Jain, David Levy, David Bushinsky, Guohua Zeng, and Shuyuan Yeh Wei ZhuWei Zhu More articles by this author , Wenbiao RenWenbiao Ren More articles by this author , Chawnshang ChangChawnshang Chang More articles by this author , Edward M. MessingEdward M. Messing More articles by this author , Jean V. JosephJean V. Joseph More articles by this author , Rajat JainRajat Jain More articles by this author , David LevyDavid Levy More articles by this author , David BushinskyDavid Bushinsky More articles by this author , Guohua ZengGuohua Zeng More articles by this author , and Shuyuan YehShuyuan Yeh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Kidney stone is a common disorder that poses a significant health care burden. The incidence of kidney stone disease is lower in premenopausal women than age-matched men, as well as in female animal models with renal calcium oxalate (CaOx) crystal deposition. However, it is unclear if this gender difference is related to altered estrogen/estrogen receptor (ER) signaling. METHODS: Kidney and liver cell lines, HK-2, HKC-8, HepG2, and HEK-293, were used. The shRNA and cDNA of NOX2 and ERβ were applied to study their functions. Hydrogen Peroxide Assay and DHE Staining were used to detect Oxalate treatment effects and ROS in renal cells. The q-PCR and western blot assays were applied to assess the RNA and protein expressions, respectively. ERβ knockout (ERβKO,) and WT female mice were used to compare CaOx formation. Effects of ERβ antagonist was tested in hydroxyl-L-proline (HLP) diet induced CaOx crystal deposition rat model. RESULTS: CaOx is one major composition accounts for majority of kidney stones. We found that ERβ signals could suppress hepatic oxalate biosynthesis via transcriptional up-regulation of the glyoxylate aminotransferase (AGT1) expression in liver cells. Results from renal cell lines also showed that ERβ could function via suppressing the oxalate-induced injury to reduce the reactive oxygen species (ROS) production and decrease the renal calcium oxalate (CaOx) deposition. Mechanism studies showed that ERβ could suppress the oxalate-induced oxidative stress via transcriptional suppression of the NADPH oxidase subunit 2 (NOX2) via binding to the NOX2 5′ promoter. We further applied two in vivo animal models rat fed with 5% HLP diet-induced renal CaOx deposition. Our data demonstrated that mice lacking ERβ (ERβKO) as well as mice or rats treated with ERβ antagonist PHTPP had increased urinary oxalate excretion, renal ROS production as well as renal CaOx crystal deposition. Importantly, targeting ERβ-regulated NOX2 with the NADPH oxidase inhibitor, apocynin, can reduce the renal CaOx crystal deposition in the in vivo animal model. CONCLUSIONS: Results from multiple in vitro cell lines and in vivo mouse/rat models all demonstrate that ERβ may protect against renal CaOx deposition via reducing the hepatic oxalate biosynthesis and oxidative stress-induced renal injury. Source of Funding: This work was partially supported by URMC Urology Research fund, National Natural Science Foundation of China, and George Whipple Professorship Endowment at U of Rochester © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e140-e140 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei Zhu More articles by this author Wenbiao Ren More articles by this author Chawnshang Chang More articles by this author Edward M. Messing More articles by this author Jean V. Joseph More articles by this author Rajat Jain More articles by this author David Levy More articles by this author David Bushinsky More articles by this author Guohua Zeng More articles by this author Shuyuan Yeh More articles by this author Expand All Advertisement Loading ...