Paraquat affects the differentiation of neural stem cells and impairs the function of vascular endothelial cells: a study of molecular mechanism
Paraquat affects the differentiation of neural stem cells and impairs the function of vascular endothelial cells: a study of molecular mechanism
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百草枯影响神经干细胞分化并损害血管内皮细胞功能的分子机制研究
DOI：
10.1002/tox.22723
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发表时间：
2019-04-01
影响因子：
4.5
通讯作者：
Yang, Huifang
中科院分区：
文献类型：
--
作者：
Huang, Min;Cai, Qian;Yang, Huifang
目的探讨百草枯（PQ）暴露对神经干细胞基因表达及血管内皮细胞结构和功能的影响。方法采用RNA-Seq技术检测PQ作用下人脐带血神经干细胞（HUCB-NSCs）在增殖、分化早期和分化晚期的差异表达基因。采用CCK-8、流式细胞仪、ELISA和western blot等方法检测PQ对人脐静脉内皮细胞（HUVECs）增殖、凋亡、细胞因子分泌和紧密连接蛋白表达的影响。结果PQ诱导HUCB-NSCs表达上调的基因有53个，下调的基因有61个，其中与神经干细胞分化相关的基因有7个，分别为GFap、S100 B、Oct 4、Gdf 3、Sox 1、Pax 6和Ngn 1。PQ处理显著抑制HUVECs增殖，抑制细胞因子（VEGF、BFGF）的分泌和紧密连接相关蛋白（Claudin 1、Occludin、ZO-1）的表达，并诱导明显的细胞凋亡。结论PQ可能通过影响神经干细胞分化相关基因的表达及血管内皮细胞的结构和功能，从而影响神经系统发育，导致神经系统异常。
Objective To investigate the effect of paraquat (PQ) exposure on gene expression in neural stem cells as well as structures and functions of vascular endothelial cells. Methods RNA-Seq was used to explore the differentially expressed genes in human umbilical cord blood-neural stem cells (HUCB-NSCs) at different stages (eg, proliferation, early and late differentiation) in the presence of PQ. The effects of PQ on human umbilical vein endothelial cells (HUVECs), including cell proliferation, apoptosis, cytokines secretion, and expression of tight junction proteins, were assessed with CCK-8, flow cytometry, ELISA, and western blot analysis, individually. Results A total of 53 genes were up-regulated and 61 genes were down-regulated in PQ treated HUCB-NSCs, including seven genes associated with the differentiation of neural stem cells, for example, Gfap, S100B, Oct4, Gdf3, Sox1, Pax6, and Ngn1. PQ treatment significantly reduced the proliferation of HUVECs, inhibited cytokines secretion (VEGF, BFGF) and expressions of tight junction-associated protein (Claudin 1, Occludin, ZO-1), as well as induced significant apoptosis. Conclusion Our study suggests that PQ impairs the development of nervous system by regulating the expression of genes associated with neural stem cell differentiation, as well as the structure and function of vascular endothelial cells, which together lead to abnormality in the nervous system.