Key Laboratory of Smart Animal Farming Technology, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
Inhal Toxicol. 2022;34(7-8):219-229. doi: 10.1080/08958378.2022.2083275. Epub 2022 Jun 1.
Ammonia is a toxic gas that not only causes environmental pollution, but also is harmful to human health after inhalation. Liver is an important detoxification organ that can convert external or metabolized toxic substances into nontoxic substances. However, the toxic effects of ammonia exposure on livers have not been well studied. In this study, pigs were used as an animal model and were exposed to 80 ppm ammonia (8 h during 12 days), and then, RNA-seq were conducted to explore the key genes in response to high ammonia exposure in livers. Gene set enrichment analysis (GSEA) showed that the genes associated with hypoxia, inflammatory response, and apoptosis were up-regulated in the ammonia group, but the genes associated with DNA replication, linoleic acid metabolism, and glycolysis were down-regulated. Totally, 556 differentially expressed genes (DEGs) including 54 genes that encode the transcription factors (TFs) were identified between the exposure and control groups. GO and KEGG pathway analysis suggested that these DEGs were involved in inflammatory response, oxidative stress, apoptosis, immune, and cell cycle. Furthermore, the TF-target interaction analysis showed that FOS, HIF-1α, JUNB, ATF3, REL, and KLF4 were important TFs in regulating the hepatic gene expression in response to high ammonia exposure. Altogether, our findings not only presented a comprehensive mRNA transcriptome profile of liver after high ammonia exposure, but also found some key genes and TFs that could be used to investigate the toxicity mechanism of high ammonia on livers.
氨是一种有毒气体，不仅会造成环境污染，吸入后还会对人体健康造成危害。肝脏是一种重要的解毒器官，可以将外部或代谢产生的有毒物质转化为无毒物质。然而，高浓度氨暴露对肝脏的毒性作用尚未得到充分研究。在这项研究中，猪被用作动物模型，暴露于 80ppm 氨（12 天内 8 小时），然后进行 RNA-seq 以探索肝脏对高氨暴露的关键基因。基因集富集分析（GSEA）表明，与缺氧、炎症反应和细胞凋亡相关的基因在氨组中上调，而与 DNA 复制、亚油酸代谢和糖酵解相关的基因下调。在暴露组和对照组之间总共鉴定出 556 个差异表达基因（DEGs），包括 54 个编码转录因子（TFs）的基因。GO 和 KEGG 通路分析表明，这些 DEGs 参与了炎症反应、氧化应激、细胞凋亡、免疫和细胞周期。此外，TF-靶标相互作用分析表明，FOS、HIF-1α、JUNB、ATF3、REL 和 KLF4 是调节肝脏高氨暴露后基因表达的重要 TF。总之，我们的研究结果不仅提供了高氨暴露后肝脏全面的 mRNA 转录组图谱，还发现了一些关键基因和 TF，可用于研究高氨对肝脏的毒性机制。
