The Involvement of the PI3K/AKT Pathway in Zn Alleviation of Heat Stress-Induced Damage to Broiler Jejunal Organoids

The direct involvement of the phosphatidylinositol 3-kinase (PI3K)/serine threonine kinase (AKT) signaling pathway in the alleviation of the heat stress (HS)-induced damage to the integrity and barrier function of broiler jejunal organoids (JOs) by supplemental zinc (Zn) has not been confirmed. To verify it, two experiments were conducted in the present study. In experiment 1, the optimal concentrations of PI3K/AKT inhibitor (PI3K-IN-1) or agonist (YS-49) were screened. In experiment 2, the role of PI3K/AKT in Zn alleviation of HS-induced damage to JOs was evaluated with three JO types as control groups under baseline incubation temperature (40 °C) plus a 3 (JOs types) × 3 (Zn sources) factorial design under high temperature (44 °C). The results showed that the optimal concentrations of the PI3K-IN-1 and YS-49 for effectively inhibiting and promoting (p < 0.001) phosphorylation of PI3K and AKT were 16 μmol/L and 9 μmol/L, respectively. Adding Zn, especially Zn proteinate with moderate chelation strength (Zn-Prot M), alleviated (p < 0.001) the HS-induced increases in diamine oxidase content and lactate dehydrogenase activity in the media and the HS-induced decreases in JOs budding percentage, proportions of 5-ethynyl-2′-deoxyuridine and proliferating cell nuclear antigen positive cells, and the phosphorylation of PI3K and AKT. PI3K/AKT inhibition or activation reduced or enhanced (p < 0.05) the above alleviating effect of Zn, especially Zn-Prot M. These results indicate that the PI3K/AKT signaling pathway mediated the alleviation of HS-induced damage to integrity and barrier function of broiler JOs by supplemental Zn, particularly Zn-Prot M via promotion of cell proliferation.