被撤回的出版物: Glycogen synthase kinase-3β is required for epithelial-mesenchymal transition and barrier dysfunction in mouse podocytes under high glucose conditions (Retracted article. See vol. 22, pg. 4452, 2020)

Epithelial-mesenchymal transition (EMT) is important for diabetic nephropathy (DN). Podocytes are specialized epithelial cells, which form a major component of the glomerular filtration barrier. Podocyte damage has been suggested to be the primary mechanism behind the albuminuria associated with DN. The present study aimed to determine the function of glycogen synthase kinase (GSK)-3 beta in EMT and barrier dysfunction of mouse podocytes exposed to high glucose (HG) conditions. Matured and differentiated podocytes were treated with normal glucose (NG), HG or NG + mannitol. Podocytes were also transfected with a small interfering RNA (siRNA) against GSK-3 beta or a scrambled siRNA, or were treated with lithium chloride (LiCl), a GSK-3 beta inhibitor, under NG or HG conditions. The expression levels of the epithelial cell markers, nephrin and podocin, and the myofibroblast cell markers, alpha-smooth muscle actin (SMA) and fibronectin, in podocytes by western blot analysis and immunofluorescence staining, respectively. The monolayer barrier function was assessed by albumin inflow. The phosphorylation and activity levels of GSK-3 beta were also quantified. It was observed that HG promotes EMT in podocytes, due to the increased levels of podocin and nephrin expression and the reduced alpha-SMA and fibronectin expression levels. HG also induced barrier dysfunction and increased the expression level of total GSK-3 beta, Try216-phosphorylated-GSK-3 beta and the GSK-3 beta activity in podocytes. Transfection of GSK-3 beta siRNA or treatment with LiCl reversed the HG-induced EMT and barrier dysfunction in podocytes. In conclusion, the present study determined that GSK-3 beta is required for EMT and barrier dysfunction in podocytes under HG conditions; therefore, GSK-3 beta may be a novel target for the treatment of DN.