鞣花酸调控Nrf2和NLRP3通路影响TGF-β所致AML-12细胞EMT的作用

Ellagic acid affects TGF-β-induced EMT in AML-12 cells by regulating Nrf2 and NLRP3 pathways

研究了鞣花酸(EA)对TGF-β所致小鼠AML-12正常肝细胞上皮-间质转化(EMT)的影响及其可能机制.通过细胞活力评价、细胞形态观察和细胞内ROS水平检测,评价了EA对TGF-β所致AML-12细胞EMT的作用.通过免疫荧光和免疫印迹检测了细胞内EMT标志蛋白钙黏蛋白E(E-cadherin)和波形蛋白(Vimentin)的表达;免疫印迹检测了细胞内Nrf2和NLRP3通路相关因子的表达水平.结果显示:EA显著抑制了TGF-β所致AML-12细胞EMT.进一步研究表明,EA可以诱导Nrf2入核并上调其下游抗氧化基因的表达.EA还可以下调NLRP3炎症通路相关蛋白的表达.综上所述,EA对TGF-β诱导的AML-12小鼠肝细胞EMT具有抑制作用,其机制可能与调控Nrf2抗氧化通路与NLRP3炎症通路有关.

Aiming to explore effect of ellagic acid(EA)on TGF-β-triggered epithelial mesenchymal transformation(EMT)in AML-12 mouse untransformed hepatocytes.Cell viability assay,cell morphology observation,and intracellular ROS analysis were performed to assess effects of EA on TGF-β-induced EMT in AML-12 cells.Immunofluorescence and immunoblotting were performed to detect expressions of EMT markers including E-cadherin and vimentin.Factors associated with Nrf2 anti-oxidative and NLRP3 inflammatory pathways were also detected by immunoblotting.The results revealed that EA obviously inhibited TGF-β-induced EMT in AML-12 cells.Further studies showed that EA increased nuclear translocation of Nrf2 and boosted expressions of antioxidant genes downstream of Nrf2.Moreover,EA decreased proteins related with NLRP3 inflammatory pathways.EA is capable of suppressing TGF-β-mediated EMT in AML-12 mouse hepatocytes.Modulating Nrf2 antioxidant and NLRP3 inflammatory pathway is implicated in its protective effects.