Effects of microRNA-346 on epithelial-mesenchymal transition in mouse podocytes.

Recent studies have shown that microRNA (miR)-346 regulates the expression of glycogen synthase kinase (GSK)-3β and activates the Wnt/β-catenin pathway, which regulates the differentiation of human bone marrow mesenchymal stem cells. Here, we explored whether miR-346 was involved in high glucose-induced epithelial-mesenchymal transition in mouse podocytes and examined the relationship between miR-346 and GSK-3β expression. The expression of miR-346 in podocytes was measured in the presence of different concentrations of glucose. Podocytes were transfected with miR-346 mimic or miR-346 inhibitor to test whether miR-346 affected the expression of nephrin, α-smooth muscle actin (α-SMA), and GSK-3β. Luciferase assays were performed to determine whether miR-346 directly regulated GSK-3β expression. The expression of miR-346 was significantly higher in podocytes cultured in the presence of 12.5mM glucose than in podocytes cultured in the presence of physiological glucose (5.6mM). However, culture in 25 mM glucose resulted in decreased miR-346 expression compared with culture in 12.5mM glucose. Cells transfected with miR-346 mimic showed reduced expression of α-SMA and increased expression of nephrin. Luciferase assays showed that miR-346 did not directly bind to the 3'-untranslated region of GSK-3β mRNA in mouse podocytes. The production of GSK-3β protein was markedly lower in podocytes transfected with the miR-346 mimic than in untransfected podocytes but was not altered in podocytes transfected with miR-346 inhibitor. Thus, these data demonstrated that miR-346 participated in the epithelial-mesenchymal transition in mouse podocytes under high-glucose conditions and that miR-346 could indirectly regulate the expression of GSK-3β in mouse podocytes.

Xiao J ，Liu D ，Jiao W ，Guo J ，Wang X ，Zhang X ，Lu S ，Zhao Z ... -  《-》

GSK-3β and vitamin D receptor are involved in β-catenin and snail signaling in high glucose-induced epithelial-mesenchymal transition of mouse podocytes.

Epithelial-mesenchymal transition (EMT) is recognized to play an important role in diabetic nephropathy (DN). To analyze the roles of glycogen synthase kinase 3β (GSK-3β), β-catenin and Snail signaling in high glucose (HG)-induced mouse podocytes EMT. Differentiated podocytes were divided into: the normal glucose group (NG: glucose 5.6mM), the HG groups (12.5HG: 12.5mM; 25HG: 25mM; and 50HG: 50mM of glucose), and the osmotic control group (NG+M: glucose 5.6mM and mannitol 44.4mM). GSK-3β, β-catenin and Snail were assessed using semi-quantitative RT-PCR, western blot and immunofluorescence. β-catenin and Snail pathways were assessed after down-regulating GSK-3β expression using an inhibitor (LiCl) or a small-interfering RNA (siRNA). HG increased GSK-3β, β-catenin and Snail expressions, and promoted EMT, as shown by decreased nephrin expression (epithelial marker), and increased α-SMA expression (mesenchymal marker). GSK-3β inhibitor and GSK-3β siRNA decreased β-catenin and Snail expressions, and reversed HG-induced EMT. Immunofluorescence showed that GSK-3β and β-catenin did not completely overlap; β-catenin was transferred to the nucleus in the 25HG group. VDR seems to be involved in HG-induced β-catenin nuclear translocation. Down-regulating GSK-3β expression decreased β-catenin and Snail expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3β might be a target to slow or prevent DN. © 2014 S. Karger AG, Basel.

Guo J ，Xia N ，Yang L ，Zhou S ，Zhang Q ，Qiao Y ，Liu Z ... -  《-》

MicroRNA-26b inhibits cell proliferation and cytokine secretion in human RASF cells via the Wnt/GSK-3β/β-catenin pathway.

Sun J ，Yan P ，Chen Y ，Chen Y ，Yang J ，Xu G ，Mao H ，Qiu Y ... -  《Diagnostic Pathology》

Lenticular cytoprotection, part 2: link between glycogen synthase kinase-3β, epithelial to mesenchymal transition, and mitochondrial depolarization.

Neelam S ，Brooks MM ，Cammarata PR 《MOLECULAR VISION》

Troglitazone ameliorates high glucose-induced EMT and dysfunction of SGLTs through PI3K/Akt, GSK-3β, Snail1, and β-catenin in renal proximal tubule cells.

Lee YJ ，Han HJ 《-》