Ursolic acid inhibits high glucose-induced epithelial mesenchymal transition of podocyte by mediating Wnt/β-catenin signaling pathway / 中华肾脏病杂志

ABSTRACT

Objective To observe the epithelial mesenchymal transition (EMT) of podocyte induced by high glucose,and to explore the potential protective mechanism of ursolic acid (UA).Methods The podocytes cultured in vitro were divided into four groupsnormal group (glucose 5.5 mmol/L),mannitol group (glucose 5.5 mmol/L+mannitol 19.5 mmol/L),high glucose group (glucose 25 mmol/L) and UA group (glucose 25 mmol/L + UA 5 μmol/L).Podocyte morphology changes were observed by inverted phase contract microscope.The expression of zonula occludens-1 (ZO-1) and α-smooth muscle actin (α-SMA) were detected by immunofluorescence.The expressions of β-catenin and glycogen synthesis kinase-3β (GSK3β) were detected by Western blotting.The expressions of Wnt1,Wnt3a,Wnt5a,Wnt5b and GSK3β were detected by real-time PCR.Results Podocytes showed irregular arborization shape in normal glucose and transited to longer cobblestone-like shape as mesenchyme cell by high glucose culture.Compared with normal group,the expression of ZO-1 protein was down-regulated and the expression of α-SMA was up-regulated by high glucose culture (P ＜ 0.05).The expression of Wnt5a mRNA was down-regulated;β-catenin mRNA and protein were up-regulated (P ＜ 0.05);and GSK3β protein was down-regulated by high glucose culture (P ＜ 0.05).Compared with high glucose group,ursolic acid inhibited podocyte EMT,up-regulated the expression of ZO-1 protein,Wnt5a mRNA,GSK3β (P ＜ 0.05),and down-regulated the expressions of α-SMA protein,β-catenin mRNA and protein (P ＜ 0.05).Conclusion Ursolic acid attenuates high glucose induced epithelial mesenchymal transition of podocyte by inhibiting Wnt/β-catenin signaling pathway.