Inflammation-coagulation response and thrombotic effects induced by silica nanoparticles in zebrafish embryos.
Inflammation-coagulation response and thrombotic effects induced by silica nanoparticles in zebrafish embryos.
复制标题
DOI：
10.1080/17435390.2018.1461267
复制
发表时间：
2018-06
期刊：
影响因子：
5
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Duan J;Liang S;Yu Y;Li Y;Wang L;Wu Z;Chen Y;Miller MR;Sun Z
如今，纳米技术环境健康和安全（nanoEHS）正受到越来越多的关注。我们以前发现二氧化硅纳米颗粒（SiNPs）可以诱导血管内皮损伤。然而，SiNP诱导的内皮损伤的后续毒理学反应在很大程度上仍然未知。在这项研究中，我们探讨了SiNPs在内皮细胞和斑马鱼胚胎中的炎症-凝血反应和血栓形成作用。在体外研究中，超微结构分析中观察到肿胀的线粒体和自噬体。在血管内皮细胞中，SiNPs破坏了细胞骨架组织。IL-6、IL-8、MCP-1、PECAM-1、TF和vWF等促炎和促凝血细胞因子的释放量呈剂量依赖性增加。对于体内研究，基于用于剂量测定选择的NOAEL，并且使用两种转基因斑马鱼，Tg（mpo：GFP）和Tg（fli-1：EGFP），SiNP诱导嗜中性粒细胞介导的炎症和受损的血管内皮细胞。当剂量高于NOAEL时，SiNPs显著降低斑马鱼胚胎的血流和速度，表现出血液高凝状态。邻联茴香胺染色法观察SiNPs对斑马鱼血栓形成的影响，结果显示SiNPs处理后斑马鱼红细胞聚集性增加。利用基因芯片技术筛选SiNPs诱导斑马鱼炎症-凝血反应的可能基因，并通过qRT-PCR和Western blot技术进一步验证JAK 1/TF信号通路。为了深入研究，il 6st被特定的吗啉敲除。整体原位杂交和qRT-PCR分析显示，IL 6 st基因敲除组jak 1和f3 b的表达减弱。总之，我们的数据表明，SiNPs可以通过JAK 1/TF信号通路诱导炎症-凝血反应和血栓形成。
Nowadays, nanotechnology environmental health and safety (nanoEHS) is gaining attention. We previously found that silica nanoparticles (SiNPs) could induce vascular endothelial damage. However, the subsequent toxicologic response to SiNPs-induced endothelial damage was still largely unknown. In this study, we explored the inflammation–coagulation response and thrombotic effects of SiNPs in endothelial cells and zebrafish embryos. For in vitro study, swollen mitochondria and autophagosome were observed in ultrastructural analysis. The cytoskeleton organization was disrupted by SiNPs in vascular endothelial cells. The release of proinflammatory and procoagulant cytokines including IL-6, IL-8, MCP-1, PECAM-1, TF and vWF, were markedly elevated in a dose-dependent manner. For in vivo study, based on the NOAEL for dosimetry selection, and using two transgenic zebrafish, Tg(mpo:GFP) and Tg(fli-1:EGFP), SiNPs-induced neutrophil-mediated inflammation and impaired vascular endothelial cells. With the dosage higher than NOAEL, SiNPs significantly decreased blood flow and velocity, exhibiting a blood hypercoagulable state in zebrafish embryos. The thrombotic effect was assessed by o-dianisidine staining, showed that an increasing of erythrocyte aggregation occurred in SiNPs-treated zebrafish. Microarray analysis was used to screen the possible genes for inflammation–coagulation response to SiNPs in zebrafish, and the JAK1/TF signaling pathway was further verified by qRT-PCR and Western blot assays. For in-deepth study, il6st was knocked down with specific morpholinos. The whole-mount in situ hybridization and qRT-PCR analysis showed that the expression jak1 and f3b were attenuated in il6st knockdown groups. In summary, our data demonstrated that SiNPs could induce inflammation–coagulation response and thrombotic effects via JAK1/TF signaling pathway.
登录
查看更多内容
影响因子：
5.4
作者：
Etheridge, Michael L.;Campbell, Stephen A.;Erdman, Arthur G.;Haynes, Christy L.;Wolf, Susan M.;McCullough, Jeffrey
通讯作者：
McCullough, Jeffrey
影响因子：
5
作者：
Khatri, Madhu;Bello, Dhimiter;Woskie, Susan
通讯作者：
Woskie, Susan
影响因子：
5
作者：
Jun, Eun-Ah;Lim, Kyung-Min;Chung, Jin-Ho
通讯作者：
Chung, Jin-Ho
影响因子：
2.1
作者：
Jiang, Lizhen;Li, Yanbo;Sun, Zhiwei
通讯作者：
Sun, Zhiwei
影响因子：
3.8
作者：
Mendoza, Alvaro;Torres-Hernandez, Jose A.;Lawrence, David A.
通讯作者：
Lawrence, David A.