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Wilms tumor 1 (WT1) and \u03b2\u2010catenin are two master regulators that play opposing roles in podocyte biology and mutually antagonize each other. However, exactly how \u03b2\u2010catenin inhibits WT1 remains incompletely understood. In this study, we demonstrated the role of miR\u2010466o\u20103p in mediating \u03b2\u2010catenin\u2010triggered podocyte injury by targeting WT1. The expression of miR\u2010466o\u20103p was upregulated in cultured podocytes after \u03b2\u2010catenin activation and in glomerular podocytes in adriamycin (ADR) nephropathy, remnant kidney after 5\/6 renal ablation, and diabetic kidney disease. Bioinformatics analysis and luciferase reporter assay confirmed that miR\u2010466o\u20103p directly targeted WT1 mRNA. Furthermore, overexpression of miR\u2010466o\u20103p downregulated WT1 protein and promoted podocyte injury in vitro. Conversely, inhibition of miR\u2010466o\u20103p alleviated \u03b2\u2010catenin\u2010induced podocyte dysfunction. In mouse model of ADR nephropathy, overexpression of miR\u2010466o\u20103p inhibited WT1, aggravated podocytes injury and deteriorated proteinuria. In contrast, inhibition of renal miR\u2010466o\u20103p by antagomiR, either prior to or after ADR injection, substantially restored WT1, alleviated podocytes injury and reduced renal fibrosis. These studies reveal a critical role for miR\u2010466o\u20103p, a novel microRNA that has not been characterized previously, in mediating \u03b2\u2010catenin\u2010triggered WT1 inhibition. Our findings also uncover a new pathogenic mechanism by which \u03b2\u2010catenin promotes podocyte injury and proteinuria in glomerular diseases.<\/jats:p>","DOI":"10.1096\/fj.202000464r","type":"journal-article","created":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T08:09:53Z","timestamp":1599293393000},"page":"14424-14439","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MicroRNA\u2010466o\u20103p mediates \u03b2\u2010catenin\u2010induced podocyte injury by targeting Wilms tumor 1"],"prefix":"10.1096","volume":"34","author":[{"given":"Qiyan","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research National Clinical Research Center of Kidney Disease Division of Nephrology Nanfang Hospital Southern Medical University Guangzhou 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