College of Veterinary Medicine, Northeast Agricultural University; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin 150030, China.
College of Life Science, Northeast Agricultural University, Harbin 150030, China.
Sci Total Environ. 2021 Jun 1;771:145407. doi: 10.1016/j.scitotenv.2021.145407. Epub 2021 Jan 26.
Hydrogen sulfide (HS) is an environmental contaminant to cause the airway damage. The release of macrophage extracellular traps (METs) is the mechanism of immune protection to harmful stimulation via microRNAs, but excessive METs cause the injury. However, few studies have attempted to interpret the mechanism of an organism injury due to HS via METs in chickens. Here, we investigated the transcriptome profiles, pathological morphologic changes and METs release from chicken trachea after HS exposure. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 10 differentially expressed genes were related to the METs release, the MAPK and insulin signaling pathways. Morphological and immunofluorescence analysis showed that HS caused airway injury and MET release. HS activated the targeting effect of miRNA-15b-5p on activating transcription factor 2 (ATF2). Western blotting and real time quantitative PCR results showed that HS down-regulated the levels of dual specificity protein phosophatase1 (DUSP1) but up-regulated p38 MAP Kinase (p38) in the MAPK signal pathway. And the expression of phosphoinositide-dependent protein kinase 1 (PDK1), serine/threonine kinase (Akt), and protein kinase ζ subtypes (PKCζ) in the insulin signal pathway were increased after HS exposure. These promoted the release of myeloperoxidase (MPO) and degradation histone 4 (H4) to induce the release of METs. Taken together, miR-15b-5p targeted ATF2 to mediate METs release, which triggered trachea inflammatory injury via MAPK and insulin signals after HS exposure. These results will provide new insights into the toxicological mechanisms of HS and environmental ecotoxicology.
硫化氢（HS）是一种环境污染物，可导致气道损伤。巨噬细胞细胞外陷阱（METs）的释放是通过 microRNAs 对有害刺激产生免疫保护的机制，但过多的 METs 会导致损伤。然而，很少有研究试图通过鸡的 METs 解释 HS 导致机体损伤的机制。在这里，我们研究了 HS 暴露后鸡气管的转录组谱、病理形态变化和 METs 释放。基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析显示，10 个差异表达基因与 METs 释放、MAPK 和胰岛素信号通路有关。形态学和免疫荧光分析表明，HS 导致气道损伤和 MET 释放。HS 激活了 microRNA-15b-5p 对激活转录因子 2（ATF2）的靶向作用。Western blot 和实时定量 PCR 结果表明，HS 下调了 MAPK 信号通路中双特异性蛋白磷酸酶 1（DUSP1）的水平，但上调了 p38 MAP 激酶（p38）。胰岛素信号通路中的磷酸肌醇依赖性蛋白激酶 1（PDK1）、丝氨酸/苏氨酸激酶（Akt）和蛋白激酶 ζ 亚型（PKCζ）的表达在 HS 暴露后增加。这些促进了髓过氧化物酶（MPO）的释放和组蛋白 4（H4）的降解，从而诱导 METs 的释放。总之，miR-15b-5p 靶向 ATF2 介导 METs 的释放，HS 暴露后通过 MAPK 和胰岛素信号触发气管炎症损伤。这些结果将为 HS 的毒理学机制和环境生态毒理学提供新的见解。
