The IL17 signaling pathway: A potential signaling pathway mediating gill hyperplasia and inflammation under ammonia nitrogen stress was identified by multi-omics analysis

Ammonia nitrogen is extremely toxic to aquatic animals, and is also the most common pollutant in the aquatic environment. In order to investigate the effect of high concentration of ambient ammonia nitrogen on fish gills, two groups, including a high ammonia group (T group: TAN = 2.5 mg/L, 10 % 96 h LC50) and a control group (Z group: total ammonia nitrogen (TAN) = 0 mg/L) were set up in this study. The effects of chronic ammonia stress on the gills of Pelteobagrus fulvidraco were investigated by histopathological, enzymatic, transcriptomic and proteomic analyses after 28 d of stress at different ammonia nitrogen concentrations. Histopathological observations revealed significant inflammatory cell infiltration, necrotic and abscission at the base of the gill filaments, and massive proliferation of cells at the base of the gill lamellae. Ammonia nitrogen stress led to increased reactive oxygen species (ROS) content and decreased catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) activities in gills, indicating significant oxidative stress in gills. And further transcriptomic analysis revealed that 807 differential expression genes (DEGs) were generated in the gills, of which 587 DEGs were up-regulated and 220 DEGs were down-regulated. In addition, proteomics analysis identified 1073 differential expression proteins (DEPs) in gills, including 983 up- and 90 down-regulated DEPs. Pathway enrichment analysis of the DEGs and DEPs revealed that multiple inflammation-related signaling pathways were activated in the gill, including the significantly enriched IL17 signaling pathway. This suggests that IL17 signaling pathway might have a significant impact during signaling transduction. Further analysis of network regulation by mapping DEGs and DEPs to KEGG pathway revealed that IL17 signaling pathway mediated inflammation and cell proliferation in gills under ammonia stress. The results of this study provided new insights into the response of fish gills to ammonia nitrogen stress, and the IL17 signaling pathway may be a potential therapeutic target for reducing ammonia nitrogen gill toxicity.