Long noncoding RNA MEG3 suppresses podocyte injury in diabetic nephropathy by inactivating Wnt/β-catenin signaling

Background: Diabetic nephropathy (DN) is one of the principal complications of diabetes and podocyte injury plays an important role in the DN pathogenesis. Wnt/beta-catenin signaling overactivation confers podocyte injury and promotes multiple types of renal disease. However, the underlying mechanism of Wnt/beta-catenin signaling activation in DN progression has not been fully elucidated. Long noncoding RNA (lncRNA) is a large class of endogenous RNA molecules lacking functional code capacity and which participates in the pathogenesis of human disease, including DN. Method: A diabetes model was constructed by intraperitoneal injection of Streptozotocin in rats. The MPC5 cells were used to create the in vitro model. Western blot and Quantitative reverse-transcriptase-PCR were used to examine the expression of protein and mRNA. The migrated capacity was analyzed by Transwell migration assay. The cell viability was detected by CCK8. Results: In the present study, we revealed the association of lncRNA Maternally Expressed Gene 3 (MEG3) with aberrant activation of Wnt/beta-catenin signaling and the role of MEG3/Wnt axis in podocyte injury. We found that high glucose (HG) treatment suppressed MEG3 expression in cultured podocytes, activated Wnt/beta-catenin signaling and caused podocyte injury as indicated by the downregulation of podocyte-specific markers (podocin and synaptopodin) and the upregulation of snail1 and alpha-smooth muscle actin. Overexpression of MEG3 attenuated HG-induced podocyte injury by reducing Wnt/beta-catenin activity, repressing cell migration, reactive oxygen species production and increasing the viability of podocytes. Furthermore, we provided evidences that restoration of Wnt/beta-catenin signaling by specific agonist impeded the protective effect of MEG3 on podocyte injury. Current results demonstrated that MEG3/Wnt axis plays an important role in fostering podocyte injury and may serve as a potential therapeutic target for the treatment of DN. Conclusion: lncRNA MEG3 ameliorates podocyte injury in DN via inactivating Wnt/beta-catenin signaling.