α-klotho Antagonizes The Effect Of Leptin On Mice Podocytes Injury

Objective To investigate the effect of leptin on mice podocytes injury, and α-klotho might antagonize this effect.Methods Podocyte were incubated with medium alone, medium with leptin(15ng/ml) or medium with α-klotho(0.1μg/ml) and leptin(15ng/ml), respectively.The expression of nephrin, podocin, podoplanin and podocalyxin of MPC determined by real-time PCR and Western blot; The expression of Wnt2b、Wnt5a、Wnt6、Wnt7a of MPC determined by real-time PCR and the expression of phosphorylation-β-catenin and total-β-catenin of MPC determined by Western blot.Results The m RNA and protein expression of podocin,nephrin,podocalyxin,podoplanin were significantly down-regulated by leptin(15ng /ml). Compared with the control group,the inhibition rates of podocin,nephrin,podocalyxin,podoplanin protein expression in the leptin group were 24%、25%、25% and 23%,respectively(P<0.05), and the inhibition rates of their m RNA were 42%、27%、39%、24%,respectively( P<0.05).α-klotho significantly up-regulated the down-regulation of podocin. nephrin, podocalyxin,podoplanin induced by leptin.Compared with the leptin group, the protein expression of podocin,nephrin,podocalyxin,podoplanin were up-regulated to 1.36、1.25、1.29 and 1.22 times, respectively( P<0.05),their m RNA expression were up-regulated to 1.77 、 1.48 、 1.66 、 1.26 times,respectively( P<0.05). Leptin(15ng /ml) can significantly activate Wnt/β-catenin signaling pathway. Compared with the control group, m RNA expression of Wnt2b、Wnt5a、Wnt6、Wnt7a were up-regulated 2.06、1.72、2.14、1.59 times, respectively( P<0.05). The inhibition rates of phospho-β-catenin in the leptin group was 26%( P<0.05). α-klotho significantly inhibited the activation of Wnt/β-catenin signaling pathway induced by leptin. Compared with the leptin group, the inhibition rates of Wnt2b、Wnt5a、Wnt6、Wnt7a m RNA in the α-klotho and leptin costimulated group were 42%、28%、43%、30%, respectively( P< 0.05). The phosphor-β-catenin in theα-klotho and leptin costimulated group were up-regulated 1.27 times( P<0.05).Conclusion Leptin can cause podocyte injury through Wnt/β-catenin signaling pathway, α-klotho can reverse this effect induced by leptin.