Effect of eriodictyol on proliferation,oxidative stress response and TGF-β1/Smad signaling pathway activation of human skin fibroblasts induced by TGF-β1
Objective To explore the effect of eriodictyol on proliferation,oxidative stress response and TGF-β1/Smad signaling pathway activation of human skin fibroblasts(HSF)induced by transforming growth factorβ1(TGF-β1).Methods HSF was assigned to control group,model group,eriodictyol low-dose group,eriodictyol medium-dose group,eriodictyol high-dose group,or SB-431542 group.The control group did not received any treatment,whereas the model group received intervention for 24 hours with 5 ng/mL TGF-β1,and the eriodictyol low-,medium,and high-dose groups received intervention for 24 hours with 40 μmol/L,80 μmol/L,and 160 μmol/L eriodictyol and 5.0 ng/mL TGF-β1 simultaneously,respectively;in addition,the SB-431542 group received intervention for 24 hours with 10 μmol/L SB-431542 and 5.0 ng/mL TGF-β1 simultaneously.The HSF cell activity,α-smooth muscle actin(α-SMA)protein expression,reactive oxygen species(ROS)content,superoxide dismutase(SOD)activity,and mRNA expressions of TGF-β1,α-SMA,collagen type Ⅰ(ColⅠ),collagen type Ⅲ(ColⅢ),matrix metalloproteinase 2(MMP2),as well as TGF-β1 protein expression were detected in various groups.The protein expressions of Smad2,Smad3,phosphorylated Smad2(p-Smad2),and phosphorylated Smad3(p-Smad3)of HSF were detected in the control group,the model group,and the eriodictyol medium-dose group.Results Compared with the control group,the model group exhibited increased HSF cell activity and elevated α-SMA protein expression,increased ROS content while decreased SOD activity,up-regulated mRNA expressions of TGF-β1,α-SMA,ColⅠ,ColⅢ,and MMP2,and up-regulated protein expressions of TGF-β1,Smad2,Smad3,p-Smad2,and p-Smad3(P＜0.05).Compared with the model group,the eriodictyol various-dose groups and the SB-431542 group yielded decreased HSF cell activity,ROS content,while increased SOD activity,and down-regulated mRNA expressions of α-SMA,ColⅠ,ColⅢ,and MMP2,as well as down-regulated protein expression of TGF-β1;in addition,eriodictyol medium-and high-dose groups and the SB-431542 group depicted decreased protein expression of α-SMA in HSF cell,and the eriodictyol medium-dose group and the SB-431542 group interpreted down-regulated protein expressions of Smad2,Smad3,p-Smad2,and p-Smad3(P＜0.05).The eriodictyol low-,medium-,and high-dose groups presented as decreased HSF cell activity,α-SMA protein expression,and ROS content successively,and increased SOD activity successively,as well as decreased mRNA expressions of α-SMA,ColⅠ,ColⅢ successively(P＜0.05).Conclusion Eriodictyol may inhibit fibrosis of HSF cell induced by TGF-β1 in a dose-dependent manner by inhibiting oxidative stress response and the activation of TGF-β1/Smad pathway.
万方数据
维普
