Differential tissue regulation of nrf2/keap1 crosstalk in response to Aeromonas infection in Nile tilapia: a comparative study

Abstract

The antioxidant and detoxification systems involve intricate pathways in which nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) play pivotal roles. In the basal state, reactive oxygen species are generated and neutralized in a balanced manner. However, stressors can disrupt this equilibrium, resulting in oxidative stress and cellular damage. In this study, we analyzed the expression of nrf2 and keap1 in Nile tilapia (Oreochromis niloticus) under homeostasis and challenge with Aeromonas hydrophila. During homeostasis, the predominant expression of nrf2 was observed in the liver, blood, muscle, gut, and gills, while keap1 was highly expressed in the brain, liver, blood, spleen, eye, head kidney, and gills. After the challenge, the spleen demonstrated the highest keap1 expression, while the liver displayed the highest nrf2 levels among the tissues examined. Apparently, our findings suggest that the spleen may be susceptible to initial damage following infection, leading to the manifestation of the first lesion. This susceptibility could be attributed to the spleen’s high expression of keap1, acting as a negative regulator of nrf2. Notably, a positive correlation was observed between nrf2 and keap1 expression in several tissues, with the strongest association observed in the blood, gills, and head kidney under both normal and inflammatory conditions. Our findings indicate that blood may serve as a crucial mediator of Nrf2/Keap1 signaling in tissues like the liver and gut during normal and inflammatory states. By shedding light on the altered expression and correlation of nrf2 and keap1 in various tissues, this study elucidates their potential connection to antioxidant and immune responses, as well as the pathological features of A. hydrophila infection.