You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology II1 Apr 2018MP24-14 SLC26A6 UNDERLIES VITAMIN D3 MEDIATED INTESTINAL OXALATE SECRETION AND KIDNEY CAOX CRYSTAL FORMATION VIA VDR-MIR-125B-SLC26A6 BASED MECHANISMS Kun Tang, Haoran Liu, Tao Ye, Xifeng Sun, Hua Xu, and Zhangqun Ye Kun TangKun Tang More articles by this author , Haoran LiuHaoran Liu More articles by this author , Tao YeTao Ye More articles by this author , Xifeng SunXifeng Sun More articles by this author , Hua XuHua Xu More articles by this author , and Zhangqun YeZhangqun Ye More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.767AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent evidence has indicated that elevated serum 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3] resulted in an increased risk of calcium oxalate (CaOx) kidney stones. Although vitamin D3 (VitD3)-induced hypercalciuria has been well-characterized, the potential regulatory mechanisms of oxalate metabolism are unclear. Although vitamin D3 (VitD3)-induced hypercalciuria has been well-characterized, the potential regulatory mechanisms of oxalate metabolism are unclear. METHODS ChIP assay and luciferase assay demonstrated that VDR suppressed Slc26a6 expression via directly regulating miR-125b. RESULTS Here, we showed that VitD3 mediated intestinal oxalate secretion and CaOx stone formation via a VDR-miR-125b-Slc26a6-based pathway in vivo and in vitro. First, we demonstrated that VitD3 regulated intestinal oxalate secretion and promoted glyoxylate-induced CaOx crystals formation in a VDR-dependent manner. Using miRNA microarray analysis, we found that miR-125b was significantly induced by 1,25-(OH)2D3 in Caco-2 cells. Chromatin immunoprecipitation assays demonstrated VDR-positive transcriptional activation of miR-125b. MiR-125b in turn inhibited VDR by targeting its 3’-UTR. Notably, this negative feedback loop was broken by the single nucleotide polymorphisms (SNP) rs55774542 in the interaction between miR-125b and VDR 3’-UTR, which altered susceptibility to kidney stones. Additionally, we found that miR-125b regulated endogenous 1,25-(OH)2D3 levels by directly targeting CYP24A1. Luciferase assays verified that miR-125b directly targeted the 3’-UTR of Slc26a6. CONCLUSIONS Together, our results defined a novel signaling cascade in VitD3-mediated intestinal oxalate imbalance via regulation of the VDR-miR-125b-Slc26a6 pathway, which promoted CaOx crystals formation. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e295 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kun Tang More articles by this author Haoran Liu More articles by this author Tao Ye More articles by this author Xifeng Sun More articles by this author Hua Xu More articles by this author Zhangqun Ye More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...