EIF2B5表达下调的人星形胶质细胞与人神经元在内质网应激后细胞存活及miRNA表达的差异  

The Differing Fortunes and miRNA Clusters Between Human Astrocytes and Neurons After Endoplasmic Reticulum Stress With Downregulation of EIF2B5

作　　者：陈娜[1,2] 王静敏[1] 姜玉武[1] 吴晔[1] CHEN Na;WANG Jing-Min;JIANG Yu-Wu;WU Ye(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Pediatrics,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]北京大学第一医院儿科,北京100034 [2]首都医科大学附属北京天坛医院儿科,北京100070

出　　处：《生物化学与生物物理进展》2022年第11期2230-2239,共10页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81171065,30872793)资助项目。

摘　　要：目的探讨白质消融性白质脑病中胶质细胞选择性受累而神经元受累轻微的原因。方法将EIF2B5-RNAi表达载体转染至人星形胶质细胞和人神经元,检测基础状态下及内质网应激(endoplasmic reticulum stress,ERS)后细胞凋亡和活力,检测参与ERS调控的已知和未知miRNA,筛选EIF2B5-RNAi人星形胶质细胞在ERS后miRNA变化。结果与EIF2B5-RNAi人神经元相比,星形胶质细胞自发凋亡及细胞活力下降。较之神经元,更多miRNA参与星形胶质细胞ERS刺激后的调控,EIF2B5-RNAi组参与调控的miRNA数目显著减少。聚类分析发现,5条已知miRNA是通路连接的关键组分。结论人星形胶质细胞在ERS后可能更加依赖众多促细胞增殖分化的miRNA修复,而EIF2B5-RNAi人星形胶质细胞存在自发凋亡,ERS后严重减少的miRNA可能导致细胞无法存活。Objective Human astrocytes and human neurons were transfected with EIF2B5-RNAi vectors or blank as cell model to investigate the causes that white matter glial cells selectively involved in vanishing white matter disease.Methods Apoptosis and cell viability were measured in human astrocytes and neurons with EIF2B5-RNAi or blank vector before or after the stimulation of endoplasmic reticulum stress(ERS).The sequence of known and unknown microRNAs was performed to screen those participated in regulating the response of ERS.Results Under the baseline condition,apoptosis rates were detected higher in human astrocytes with EIF2B5-RNAi and cell viability decreased significantly than the wild-type and neurons.More pieces of miRNAs regulated the ERS rescue in astrocytes with blank vectors than the EIF2B5-RNAi group.In the cluster analysis,5 pieces of miRNAs were identified as key components in pathway network.Conclusion The recovery of human astrocytes from ERS may be more dependent on the numerous miRNAs than neurons for cell proliferation and differentiation.The eroded clusters of miRNAs may promote spontaneous apoptosis and cell viability decrease in human astrocytes with EIF2B5-RNAi.As a result,it reduced the chance of survival in human astrocytes with EIF2B5-RNAi after ERS crisis.

关 键 词：白质消融性白质脑病 人星形胶质细胞 人神经元 内质网应激 凋亡 miRNA表达差异 

分 类 号：R72[医药卫生—儿科]