Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China.
Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, China.
Physiol Genomics. 2021 Mar 1;53(3):116-124. doi: 10.1152/physiolgenomics.00100.2020. Epub 2021 Jan 18.
Phenanthrene (Phe) is a model compound in polycyclic aromatic hydrocarbon (PAH) research. Reportedly, Phe treatment induced oxidative stress and histological disorders to liver. In this study, to further explore the molecular responses of liver to Phe exposure, transcriptome sequencing was applied to compare mRNA transcription profiles between Phe treatment and the control. Compared with the control, 1,581 and 1,428 genes were significantly upregulated and downregulated in Phe treatment, respectively. Further analysis revealed that Phe treatment mainly upregulated genes in Ras-MAPK and PI3K-akt signaling pathways, which represented insulin resistance and further activated the FOXO signaling pathway. The triacylglycerol biosynthesis was promoted but the gluconeogenesis process was inhibited in response to Phe treatment, demonstrating that Phe exposure disturbed the sugar and lipid metabolism. Moreover, Phe treatment upregulated the Apelin-APJ and ErbB signaling pathways, promoting angiogenesis in liver. Insulin resistance, promoted triacylglycerol biosynthesis, and angiogenesis might explain the molecular mechanisms underlying carcinogenic toxicity of Phe. Overall, this study provides new insights to understand the environmental risk of Phe to fishes.
菲（Phe）是多环芳烃（PAH）研究中的一种模型化合物。据报道，Phe 处理会导致肝脏氧化应激和组织学紊乱。在这项研究中，为了进一步探索肝脏对 Phe 暴露的分子反应，我们应用转录组测序来比较 Phe 处理和对照组之间的 mRNA 转录谱。与对照组相比，Phe 处理组分别有 1581 个和 1428 个基因显著上调和下调。进一步分析表明，Phe 处理主要上调了 Ras-MAPK 和 PI3K-akt 信号通路中的基因，这代表了胰岛素抵抗，并进一步激活了 FOXO 信号通路。三酰基甘油的生物合成受到促进，但糖异生过程受到抑制，表明 Phe 暴露扰乱了糖和脂质代谢。此外，Phe 处理上调了 Apelin-APJ 和 ErbB 信号通路，促进了肝脏的血管生成。胰岛素抵抗、促进三酰基甘油合成和血管生成可能解释了 Phe 致癌毒性的分子机制。总的来说，这项研究为理解 Phe 对鱼类的环境风险提供了新的见解。
