乏氧诱导的miR-210表达通过BDNF/NF-κB/自噬信号途径促进成纤维细胞存活

MiR-210 Protected Fibroblasts from Hypoxia by BDNF/NF-κB/Autophagy Pathway

目的乏氧环境可以引起细胞损伤,microRNA-210(miR-210)在乏氧环境下反应增强,保护细胞免受损伤。本研究我们探讨miR-210对乏氧条件下人皮肤成纤维细胞GM0639存活的影响。方法用自噬抑制剂3-甲基腺嘌呤(3MA)和ROS清除剂N-乙酰半胱氨酸(NAC)研究乏氧条件下的自噬、ROS产生和凋亡。通过测定谷胱甘肽/谷胱甘肽二硫键比值(GSH/GSSG),研究miR-210的抗氧化作用。结果与常氧条件下相比,乏氧可诱导细胞凋亡、ROS生成和自噬的发生。乏氧条件下,乏氧条件下miR-210表达降低可增加细胞凋亡和ROS生成。miR-210干扰后,脑源性神经营养因子(BDNF)增加。NF-κB受抑制后,细胞自噬水平减弱。结论miR-210/BDNF/NF-κB信号通路在乏氧条件下保护成纤维细胞免于凋亡,这与自噬水平的增加和ROS生成减少有关。

Objective Hypoxia is one stress condition which induced cell damage.MicroRNA-210(miR-210)was showed to increase under hypoxic treatment,which protected cell from injury.Here,we studied effect of miR-210 on fibroblasts survival under hypoxic conditions.Methods Human skin fibroblasts GM0639 were used.The autophagy inhibitor,3-methyladenine(3MA),and ROS scavenger,N-acetyl-cysteine(NAC),were used to study autophagy,ROS production and apoptosis under hypoxic conditions.The antioxidant effect of miR-210 was studied based on the ratio of glutathione to glutathione disulfide(GSH/GSSG).Results Hypoxia induced apoptosis,ROS production and autophagy compared to that under normoxic conditions.Apoptosis and ROS production were increased with miR-210 interfering under hypoxic conditions.Brain-derived neurotrophic factor(BDNF)was increased after miR-210 interfering.NF-κB inhibition was decreased autophagy.Conclusion these suggested that miR-210/BDNF/NF-κB signaling protected fibroblasts from apoptosis under hypoxia,which was related with increased autophagy and lowed ROS production.