文章摘要
张舒纯,张 昕,李景云,池 霞,童梅玲.NTN1调控ERK信号通路拮抗PCBs暴露致视网膜神经节细胞发育异常[J].南京医科大学学报,2021,(4):496~502
NTN1调控ERK信号通路拮抗PCBs暴露致视网膜神经节细胞发育异常
NTN1 antagonizes the abnormal development of retinal ganglion cells caused by PCBs exposure by regulating ERK signaling pathway
投稿时间:2020-08-08  
DOI:10.7655/NYDXBNS20210404
中文关键词: NTN1  RGC⁃5细胞  PCB1254  ERK信号通路  细胞增殖
英文关键词: NTN1  RGC⁃5  PCB1254  ERK signaling pathway  cell proliferation
基金项目:国家自然科学基金面上项目(81670900);江苏省重点研发计划社会发展项目(BE2018615);南京市科技发展一般项目(YKK19115)
作者单位
张舒纯 南京医科大学附属妇产医院(南京市妇幼保健院)儿童保健科江苏 南京 210004 
张 昕 南京医科大学附属妇产医院(南京市妇幼保健院)儿童保健科江苏 南京 210004 
李景云 南京医科大学附属妇产医院(南京市妇幼保健院)医学研究中心江苏 南京 210004 
池 霞 南京医科大学附属妇产医院(南京市妇幼保健院)儿童保健科江苏 南京 210004 南京医科大学儿科学院江苏 南京 210029 
童梅玲 南京医科大学附属妇产医院(南京市妇幼保健院)儿童保健科江苏 南京 210004 
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中文摘要:
      目的:研究轴突导向因子?1(netrin?1,NTN1)在拮抗多氯联苯(polychlorinated biphenyls,PCBs)暴露致视网膜神经节细胞RGC?5发育异常的作用及机制。方法:采用RT?qPCR和Western?blot检测PCBs暴露后RGC?5细胞的NTN1及ERK信号分子的表达水平;利用NTN1小干扰RNA及NTN1过表达慢病毒感染RGC?5细胞,分别为si?NTN1组和NTN1过表达+PCB1254组,同时设立阴性对照组、空载慢病毒+PCB1254组、PCB1254组和空白组,采用CCK?8法检测细胞增殖,流式细胞仪检测细胞周期、细胞凋亡,RT?qPCR及Western blot检测ERK信号分子的表达水平。结果:①PCB1254暴露后,RGC?5细胞内NTN1及p?ERK的表达显著减少;②NTN1沉默会导致 RGC?5细胞活力降低和S期阻滞;NTN1 沉默显著抑制ERK信号分子的磷酸化;③NTN1过表达可以挽救PCB1254 暴露后RGC?5 细胞的增殖活力,使S期细胞比例减少,同时ERK磷酸化水平升高。结论:NTN1可以通过调控ERK信号通路来拮抗PCB1254暴露所致的视网膜神经节细胞增殖能力下降,使S期细胞比例减少,缓解PCBs对视网膜发育的毒性作用。
英文摘要:
      Objective:To investigate the effects and mechanisms of netrin?1(NTN1)in antagonizing polychlorinated biphenyls(PCBs)toxicity in retinal ganglion cells RGC?5. Method:RT?qPCR and Western blot were used to detect the expression levels of NTN1 and ERK signaling molecules in RGC?5 cells after exposure to PCB1254;NTN1 small interfering RNA and NTN1 overexpression lentivirus were used to transfect RGC?5 cells,and control groups were set as negative control group and empty lentivirus group,and treated with or without PCB1254. Cell proliferation was detected by CCK?8 assay,cell cycle and apoptosis were detected by flow cytometry,and expression levels of ERK signal molecules were detected by RT?qPCR and Western blot. Results:①After exposure to PCB1254,the expression levels of NTN1 and p?ERK in RGC?5 cells were significantly reduced. ②NTN1 silencing reduced RGC?5 cell proliferation and led to S phase arrest;NTN1 silencing significantly inhibited the phosphorylation of ERK signaling molecules. ③NTN1 overexpression rescued the proliferation of RGC?5 cells after PCB1254 exposure,reduced the proportion of S phase cells,and increased the phosphorylation level of ERK. Conclusion:NTN1 can regulate the ERK signaling pathway to antagonize the decline in the proliferation of retinal ganglion cells caused by PCB1254 exposure,reduce the proportion of S?phase cells,and alleviate the toxic effects of PCB1254 on retinal development.
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