Comparative transcriptome analysis reveals Dusp1 as a critical regulator of inflammatory response to fly ash particle exposure in mouse
Comparative transcriptome analysis reveals Dusp1 as a critical regulator of inflammatory response to fly ash particle exposure in mouse
复制标题
比较转录组分析表明 Dusp1 是小鼠飞灰颗粒暴露炎症反应的关键调节因子
DOI：
10.1016/j.ecoenv.2019.110116
复制
发表时间：
2020
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;Chen Yiping;Namani Akhileshwar;Elshaer Mohamed;Jiang Zhinong;Shi Hongfei;Tang Xiuwen;Wang Xiu Jun
Exposure to outdoor concentrations of fine particulate matter (PM2.5) is a leading global health concern. Waste incineration emission has been recognized as a potential major contributor of ambient PM2.5. Respiratory inflammation is a central feature induced by PM2.5 exposure by inhalation. However, the molecular mechanisms are not fully understood. Dual-specificity phosphatase 1 (Dusp1) plays an instrumental role in the regulation of airway inflammation. In this study, fly ash particles (20 mg/kg BW) collected from a municipal waste incinerator in China were given to BALB/c wild-type (WT) andDusp1−/−mice by intranasal administration daily for three consecutive days. While these particles induced mild inflammation in both genotypes, a significantly higher level of serum interleukin-6 (665 pg/ml) was measured inDusp1−/−mice challenged with fly ash particles than in their WT counterparts. Genome-wide transcriptome profiling of pulmonary coding genes in response to the exposure were performed in both genotypes by RNA sequencing. We identified 487 differentially-expressed genes (DEGs) in fly ash-challengedDusp1−/−miceversustheir WT counterparts with a log2fold-change >1.5 and p < 0.05. Functional enrichment and molecular pathway mapping of the DEGs specific toDusp1−/−mice exposed to the particles revealed that the top 10 perturbed molecular pathways were associated with the immune response. Our study demonstrates the anti-inflammatory role of Dusp1 in protecting the lung against insults by fly ash particles, suggesting that Dusp1 might be a therapeutic target for the treatment of PM2.5-induced respiratory diseases.
