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The cGAS-STING pathway and its functions in immune defense and inflammatory regulation in teleost fish
Qiyang Wang1, Xiuying Cui1, Mitong Guo1
1Henan Province Engineering Research Center of Aquatic Animal Disease Control, College of Fisheries, Henan Normal University, Henan Province, PR China.
Abstract:
Cyclic GMP-AMP synthase (cGAS) could recognize double-stranded DNA in the cytoplasm and catalyze the synthesis of cyclic GMP-AMP (cGAMP). This molecule activates the endoplasmic reticulum-resident protein stimulator of interferon genes (STING), thereby initiating the TBK1 (TANK-binding kinase 1)-IRF3 (interferon regulatory factor 3) signal cascade and promoting the expression of type I interferons and various inflammatory factors. The cGAS-STING pathway serves as a fundamental signal axis for DNA recognition in the cytoplasm of vertebrates and is crucial for innate immune defense. Recent research on the cGAS-STING pathway in fish has gradually advanced, with gene cloning and analyses completed across various fish species, indicating that this pathway plays a significant role in antiviral responses in fish. However, compared to mammals, the cGAS-STING pathway exhibits relative deficiencies in molecular regulatory mechanisms, structural analyses, and in vivo functional validations in different aquatic animals. Teleost fish occupy a critical stage in vertebrate evolution. The cGAS-STING pathway in teleost fish is systematically summarized to enhance our comprehensive understanding for the innate immune regulatory network, and the potential molecular targets is to be identified for disease-resistant breeding, immune enhancement, and sustainable aquaculture practices.
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