国际眼科杂志2023，Vol.23Issue(7)：1072-1079,8.DOI:10.3980/j.issn.1672-5123.2023.7.04
吡咯烷二硫代氨基甲酸酯对TGF-β2诱导人晶状体上皮细胞EMT的抑制作用
Inhibition of pyrrolidine dithiocarbamate on transforming growth factor-beta 2 induced epithelial-mesenchymal transition in human lens epithelial cells
摘要
Abstract
AIM:To investigate the mechanism of pyrrolidine dithiocarbamate(PDTC)on transforming growth factor-beta 2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(LECs).?METHODS:LECs were treated with various doses of PDTC chemicals following TGF-β2 caused EMT on these cells.Cell proliferation and lateral migration were discovered using the CCK-8 and cell scratch test.The markers of EMT,including E-cadherin,α-SMA and nuclear factor-κB(NF-κB)signaling pathway-related expression,were tested by Western Blot as well as the changes in the expression of the apoptosis-related proteins BAX,BCL-2,Caspase-3,and Cyclin D1.?RESULTS:The proliferation and migration viability of cells in the TGF-β2 treated group was increased compared to the group without TGF-β2,and the expression of α-SMA increased whereas the E-cadherin expression decreased.With the effect of TGF-β2,NF-κB p65 and phosphorylated NF-κB p65 expression increased,the concentration of TGF-β2 that had the greatest capacity for proliferation and migration was 10 ng/mL(P<0.05).Mechanism study of PDTC-induced EMT reversal and apoptosis showed that cell viability and migratory capability were both significantly reduced after PDTC intervention;PDTC prevents IκB phosphorylation,thus inhibiting NF-κB nuclear translocation.Protein associated to the NF-κB signaling pathway,and protein expression of NF-κB/IκBα/p-IκBα/Iκκ-α/p-Iκκ-α was decreased(P<0.05),PDTC increased the expression of the pro-apoptotic protein BAX/Caspase-3,expression of the inhibitor of apoptosis protein BCL-2 and the cell cycle protein Cyclin D1 was reduced.The expression of NF-κB/IκB mRNA was reduced,expression of the apoptosis-related mRNA BAX increased,while BCL-2 reduced.?CONCLUSION:The EMT in LECs cells induced by TGF-β2 can be significantly reversed by PDTC,which may be related to the decreased expression of NF-κB p65/IκB/Iκκ-α and activation of apoptosis-related protein.PDTC can reverse EMT by inhibiting NF-κB signaling pathway and induce apoptosis of abnormally proliferated cells,which will provide new potential therapeutic agents for posterior capsular opacification(PCO)treatment.关键词
吡咯烷二硫代氨基甲酸酯/转化生长因子-β2/核因子-κB/上皮-间质转化/人晶状体上皮细胞Key words
pyrrolidine dithiocarbamate/transforming growth factor-beta 2(TGF-β2)/nuclear factor-κB(NF-κB)/epithelial-mesenchymal transition/human lens epithelial cells引用本文复制引用
姜子英,王佳伟,雷新兰,胡军..吡咯烷二硫代氨基甲酸酯对TGF-β2诱导人晶状体上皮细胞EMT的抑制作用[J].国际眼科杂志,2023,23(7):1072-1079,8.基金项目
Project for Medical Research of Wuhan Health Commission(No.WX20A15) （No.WX20A15）
School of Stomatology and Ophthalmology,Hubei University of Science and Technology(No.2020XZ36) （No.2020XZ36）
Clinical Research Institute Research Fund Project(No.AR2110D2)武汉市卫生委员会医学研究项目(No.WX20A15) （No.AR2110D2）
湖北科技学院五官医学院专项科研基金项目(No.2020XZ36) （No.2020XZ36）
临床研究机构基金项目(No.AR2110D2) （No.AR2110D2）
