You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-16 FATTY ACID BINDING PROTEIN 4 ATTENUATES MACROPHAGE AND TUBULAR CELLS CRYSTAL PHAGOCYTOSIS TO DRIVE RENAL CALCIUM OXALATE STONE DEVELOPMENT Kazumi Taguchi, Rei Unno, Teruaki Sugino, Kengo Kawase, Heiko Yang, Shuzo Hamamoto, Atsushi Okada, Marshall Stoller, Takahiro Yasui, and Tom Chi Kazumi TaguchiKazumi Taguchi More articles by this author , Rei UnnoRei Unno More articles by this author , Teruaki SuginoTeruaki Sugino More articles by this author , Kengo KawaseKengo Kawase More articles by this author , Heiko YangHeiko Yang More articles by this author , Shuzo HamamotoShuzo Hamamoto More articles by this author , Atsushi OkadaAtsushi Okada More articles by this author , Marshall StollerMarshall Stoller More articles by this author , Takahiro YasuiTakahiro Yasui More articles by this author , and Tom ChiTom Chi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urolithiasis is a significant source of morbidity, and its incidence has increased significantly over the last decades. This rise has been linked with concurrent increasing rates of obesity and hyperlipidemia. We previously reported that fatty acid binding protein (FABP) 4, a regulator of lipid metabolism, was associated with Randall’s plaques formation utilizing a transcriptomics approach in patients with urolithiasis. In this study, we elucidate the role of FABP4 function in renal calcium oxalate stone development with a transgenic mouse and gene-manipulated cell line. METHODS: 1)We compared renal and urinary crystal development between the Fabp4 knockout (KO) and wildtype (WT) mice using a nephrocalcinosis model mouse administered glyoxylate for 6 days. We further performed an RNA-sequence to analyze the gene expression patterns and pathways between the WT and KO mice to investigate the role of Fabp4 on urolithiasis. 2)An in vitro study using murine renal tubular cells (RTC) was conducted to examine calcium oxalate crystallization via Fabp4. We compared the control group with the Fabp4 knockdown group after 6 hours exposure of calcium oxalate monohydrate (COM). RESULTS: 1)The Fabp4 KO mice had significantly larger amounts of renal crystal deposits and urinary crystal than the WT mice. Additionally, the gene expression level of Ccl2 was lower in the Fabp4 KO mice than in the WT mice (figure 1A). The RNA-sequence result demonstrated that there were 16 genes commonly differentiated (>2-fold) before and after renal crystal development in the Fabp4 KO mice compared with the WT mice. These genes were associated with downregulation of antioxidant activity, IgA binding, and Toll-like receptor binding; cell-cell adhesion and neutrophil aggregation; and IgA immunoglobulin complex in Gene Ontology analysis.2)In the Fabp4 knockdown RTC, COM crystal endocytosis rate was significantly lower than the control. Gene expression levels of Ccl2 and Tumor necrosis factor were higher in the Fabp4 knockdown RTC than those of the control (figure 1B). CONCLUSIONS: We have found that Fabp4 deficiency suppresses macrophage function and crystal endocytosis in renal tubular stones, leading to stone development. These data support a causal role for FABP4 in driving urinary stone formation. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e145-e146 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazumi Taguchi More articles by this author Rei Unno More articles by this author Teruaki Sugino More articles by this author Kengo Kawase More articles by this author Heiko Yang More articles by this author Shuzo Hamamoto More articles by this author Atsushi Okada More articles by this author Marshall Stoller More articles by this author Takahiro Yasui More articles by this author Tom Chi More articles by this author Expand All Advertisement Loading ...