Transcriptomic profiling identifies a critical role of Nrf2 in regulating the inflammatory response to fly ash particles in mouse lung
Transcriptomic profiling identifies a critical role of Nrf2 in regulating the inflammatory response to fly ash particles in mouse lung
复制标题
转录组分析确定了 Nrf2 在调节小鼠肺部飞灰颗粒炎症反应中的关键作用
DOI：
10.1016/j.ecoenv.2019.110132
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发表时间：
2020-03-01
影响因子：
6.8
通讯作者：
Wang，Xiu Jun
中科院分区：
文献类型：
--
作者：
Zhang，Jingwen;Cui，Huiling;Wang，Xiu Jun
暴露于燃烧衍生的纳米颗粒被认为是一个主要的健康危害，但分子反应仍然没有得到充分的描述。转录因子红细胞2相关因子2（Nrf 2，也称为NFE 2L 2）是肺防御系统对抗颗粒物损伤的主要调节因子。然而，其下游分子过程并没有完全表征。在本研究中，BALB/c野生型（WT）和Nrf 2 −/−小鼠通过鼻内给药连续三天暴露于从中国城市垃圾焚烧炉收集的飞灰颗粒（F3-S; 20 mg/kg BW）。使用比较转录组学方法，对两种基因型的F3-S暴露的肺全局基因表达谱进行了表征。由粉煤灰颗粒诱导的WT小鼠中差异表达基因（DEG）的优势与炎症有关。对暴露于颗粒的Nrf 2 −/−小鼠特异性DEG的功能富集和分子通路作图显示，所有前10个受干扰的分子通路都与炎症反应相关。我们的研究确定了一个转录签名相关的初始肺损伤后，在飞灰暴露的小鼠，并表明抗炎作用的Nrf 2保护肺免受这种暴露。
Exposure to combustion-derived nanoparticles is recognized as a major health hazard, but the molecular responses are still insufficiently described. The transcription factor erythroid 2-related factor 2 (Nrf2, also known as NFE2L2) is a master regulator of the pulmonary defense system against insults by particulate matter. However, its downstream molecular processes are not fully characterized. In the current study, BALB/c wild-type (WT) andNrf2−/−mice were exposed by intranasal administration to fly ash particles (F3-S; 20 mg/kg BW), which were collected from a municipal waste incinerator in China, for three consecutive days. Using a comparative transcriptomics approach, the pulmonary global gene expression profiles to F3-S exposure were characterized for both genotypes. The preponderance of the differentially-expressed genes (DEGs) in WT mice induced by the fly ash particles, was related to inflammation. Functional enrichment and molecular pathway mapping of the DEGs specific toNrf2−/−mice exposed to the particles revealed that all of the top 10 perturbed molecular pathways were associated with the inflammatory response. Our study identified a transcriptional signature related to the initial pulmonary injury in mouse upon fly ash exposure, and suggests an anti-inflammatory role of Nrf2 in protecting the lung against such exposure.