Graphene oxide nanoparticles induce hepatic dysfunction through the regulation of innate immune signaling in zebrafish (Danio rerio)
Graphene oxide nanoparticles induce hepatic dysfunction through the regulation of innate immune signaling in zebrafish (Danio rerio)
复制标题
氧化石墨烯纳米颗粒通过调节斑马鱼（Danio rerio）的先天免疫信号诱导肝功能障碍
DOI：
10.1080/17435390.2020.1735552
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发表时间：
2020-03
期刊：
影响因子：
5
通讯作者：
Lu Huiqiang
中科院分区：
文献类型：
--
作者：
Xiong Guanghua;Deng Yunyun;Liao Xinjun;Zhang Jun'e;Cheng Bo;Cao Zigang;Lu Huiqiang
摘要氧化石墨烯（GO）是一种重要的纳米材料，在生物纳米技术和纳米生物医学领域具有广阔的应用前景。然而，GO对脊椎动物发育系统的毒性作用仍然知之甚少。本研究旨在探讨GO暴露对斑马鱼幼鱼和成鱼的毒性效应及其分子机制。结果表明，GO对斑马鱼胚胎的主要肝毒性表现为肝面积的显著减少和肝细胞的剂量依赖性减少。此外，GO处理后，斑马鱼胚胎中巨噬细胞和中性粒细胞的数量减少，但促炎细胞因子的表达增加。高通量RNA-Seq技术在GO诱导的斑马鱼胚胎中鉴定出314个差异表达基因（DEG），其中192个上调，122个下调。KEGG和GO功能分析显示，该基因组中类固醇激素合成、脂蛋白代谢过程和过氧化物酶体增殖物激活受体信号通路明显富集。GO处理后，大部分脂代谢基因表达下调，而大部分免疫基因表达上调。此外，GO诱导NF-κB p65进入细胞核，并增加成年斑马鱼肝脏中NF-κB p65、JAK 2、STAT 3和Bcl 2的蛋白水平。此外，药理学实验表明，抑制ROS和阻断MAPK信号可以挽救GO暴露诱导的肝毒性表型。相反，药物激活PPAR-α的表达增强了GO诱导的斑马鱼幼鱼和成鱼的肝毒性效应。综上所述，GO主要通过ROS和PPAR-α介导的天然免疫信号途径诱导斑马鱼肝功能损害。
Abstract Graphene oxide (GO) is an increasingly important nanomaterial that exhibits great promise in the area of bionanotechnology and nanobiomedicine. However, the toxic effects of GO on the vertebrate developmental system are still poorly understood. Here, we aimed to investigate the toxic effects and molecular mechanisms of GO exposure in larval and adult zebrafish. The results showed that the major hepatotoxic phenotype induced by GO in zebrafish embryos was a significant decrease in liver area and a dose-dependent decrease in the hepatocytes. Moreover, the number of macrophages and neutrophils in zebrafish embryos were reduced but the expressions of pro-inflammatory cytokines were increased after GO treatment. High through-put RNA-Seq identified 314 differentially expressed genes (DEGs) in GO-induced zebrafish embryos including 192 up-regulated and 122 down-regulated. KEGG and GO functional analysis revealed that steroid hormone biosynthesis, lipoprotein metabolic process, and PPAR signaling pathway were significantly enriched. Most of the lipid metabolism genes were down-regulated while majority of the immune genes were up-regulated after GO treatment. Moreover, GO induced NF-κB p65 into the nucleus and increased the protein levels of NF-κB p65, JAK2, STAT3, and Bcl2 in adult zebrafish liver. In addition, pharmacological experiments showed that inhibition of ROS and blocking the MAPK signaling could rescue the hepatotoxic phenotypes induced by GO exposure. On the contrary, pharmacological activation of PPAR-α expression have increased the hepatotoxic effects in GO-induced larval and adult zebrafish. Taken together, these informations demonstrated that GO induced hepatic dysfunction mainly through the ROS and PPAR-α mediated innate immune signaling in zebrafish.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
烯草酮暴露诱导斑马鱼胚胎发育免疫毒性和神经行为功能障碍
影响因子：
4.7
作者：
Xiong Guanghua;Zou Lufang;Deng Yunyun;Meng Yunlong;Liao Xinjun;Lu Huiqiang
通讯作者：
Lu Huiqiang
影响因子：
4.3
作者：
Remmerie A;Scott CL
通讯作者：
Scott CL
纳米医学中使用的纳米材料的潜在应用和人类生物安全。
DOI：
10.1002/jat.3476
发表时间：
2018-01
期刊：
Journal of applied toxicology : JAT
影响因子：
--
作者：
Su H;Wang Y;Gu Y;Bowman L;Zhao J;Ding M
通讯作者：
Ding M
DOI：
10.3390/diagnostics7030045
发表时间：
2017-07-26
期刊：
Diagnostics (Basel, Switzerland)
影响因子：
--
作者：
Forsyth R;Devadoss A;Guy OJ
通讯作者：
Guy OJ