Squalene activates Wnt/β-Catenin signaling pathway to mediate NF-κB pathway to regulate inflammatory response and disease resistance in hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu)

We previously found that squalene may influence immunity of grouper by affecting the Wnt/β-Catenin signaling pathway, but the exact mechanism is uncertain. We thus propose to interfere with the Wnt/β-Catenin signaling pathway and downstream pathways by intraperitoneal injection of PBS buffer (PBS), squalene (Sq), squalene + TWS119 (Wnt/β-Catenin signaling pathway activator, Sq + TWS119), and squalene + IWR-1 (Wnt/β-Catenin signaling pathway inhibitor, Sq + IWR-1) to initially elucidate the mechanism of squalene in hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu). The results showed: The injection test did not damage the liver structure of grouper, but Sq and Sq+TWS119 groups significantly increased the survival of Vibrio harveyi challenged and antioxidant capacity of grouper, and Sq+IWR-1 significantly decreased the survival of Vibrio harveyi challenged in grouper. The Sq and Sq+TWS119 groups activated the PI3K-Akt and Wnt/β-Catenin signaling pathway and upregulated the expression of anti-inflammatory factors in the NF-κB pathway, whereas Sq+IWR-1 inhibited the PI3K-Akt and Wnt/β-Catenin signaling pathway and upregulated the expression of pro-inflammatory factors in the NF-κB pathway. Conclusively, squalene can activate the PI3K-Akt-regulated Wnt/β-Catenin signaling pathway by binding to the interleukin 21 receptor, and the activation of Wnt/β-Catenin signaling pathway can inhibit NF-κB-mediated inflammatory response, consequently improving the immunity and disease resistance of grouper. It is expected that the regulation of NF-κB signaling pathway by Wnt/β-Catenin signaling pathway would contribute to the treatment the inflammation and inflammation-related diseases, and of course provide potential for the prevention of inflammation in aquaculture animals.