Research
| Title： | The shared immunometabolic responses between dexamethasone-induced hepatobiliary syndrome and GCRV II-caused hemorrhagic disease reveal the pivotal role of autophagy and Hsp90 activity in metabolic and infectious diseases |
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| First author： | Zheng, Siyao; Tao, Minhui; Wu, Xiaoman; Chang, Mingxian |
| Journal： | WATER BIOLOGY AND SECURITY |
| Years： | 2025 |
| DOI： | 10.1016/j.watbs.2025.100400 |
| Abstract： | Contamination by dexamethasone (DEX) in aquatic environments is expected to rise significantly as it is used in the treatment of inflammation, allergies, and autoimmune disorders, especially COVID-19. However, the underlying effects and mechanisms of DEX in leading to metabolic or infectious diseases have remained largely unexplored in teleosts. Here, we used zebrafish (Danio rerio) as a model to study the effects of DEX exposure on metabolic and infectious diseases. We found that DEX-induced hepatobiliary syndrome significantly increased susceptibility to type II grass carp reovirus (GCRV-II), which causes severe hemorrhagic disease in aquaculture. Comparative transcriptomic analysis demonstrated the shared and disease-specific immunometabolic responses among zebrafish larvae with hepatobiliary syndrome and/or GCRV-II infection. Moreover, compared with those of wild-type zebrafish, zebrafish larvae with DEX-induced hepatobiliary syndrome and/or GCRV-II infection presented increased expression of inflammatory markers (il1b), coagulation markers (fibrinogens and antithrombin III), and genes involved in autophagy, including hsp90aa. In vivo inhibition of autophagy via 3-MA and Hsp90 activity via geldanamycin markedly suppressed hepatic lipid deposition and reactive oxygen species accumulation caused by hepatobiliary syndrome and/or GCRV-II infection, thus significantly reducing the severity of disease and level of mortality induced by DEX and/or GCRV-II infection. In conclusion, our findings establish that the inhibition of autophagy and Hsp90 activity are promising therapeutic targets for DEX-induced hepatobiliary syndrome, GCRV-II infection, and DEX-induced hepatobiliary syndrome complicated with GCRV-II infection. |
