Effects of angiopoietin (Ang) 1/endothelial-enriched Tunica interna endothelial cell kinase 2 (Tie2) signaling pathway on autophagy-based neuroprotection and expression of aquaporin 4

Abstract

We investigated Ang-1/Tie2 signaling’s role in cellular autophagy-based neuroprotection and aquaporins expression. 40 mice were randomized into sham surgery group, model group, Tie2-antagonist group, and Ang-1+Tie2 agonist group, followed by observing brain pathological changes, and mRNA levels of LC3-I, LC3-II and aquaporin 4 (AQP4), together with levels of TNF-α and IL-1β. A certain regularity of brain tissue structure was observed in sham surgery group but not in model group. In Ang-1+Tie2 agonist group, the brain tissue structure was more disordered, which was ameliorated in Tie2-antagonist group, along with a proportion of intact cells. The neurological score of mice in Tie2 antagonist group was lower than Ang-1+Tie2 agonist and model groups. Levels of LC3-I and AQP4 in Tie2 antagonist group were also lower, along with higher levels of LC3-I and AQP4. LC3-II levels were higher in Tie2 antagonist group compared with those in Ang-1+Tie2 agonist and model groups. Whereas LC3-II and IL-1β/TNF-α levels in Ang-1+Tie2 agonist group were lower with higher levels of IL-1β and TNF-α. Inhibition of Ang-1/Tie2 signaling could have a restorative effect on neural function in stroke mice.