The role of the Twist1-Tie2-Angs signaling pathway in hyperoxia-induced
endothelial cell injury
Abstract
Background:Bronchopulmonary dysplasia (BPD) is a chronic lung disease
of premature infants that involves pulmonary vascular development
disorder as the main pathological feature; hyperoxia is its main
etiology. Twist1 strictly controls the development of blood vessels via
the Tie2-Angs signaling axis. However, previous research on Twist1
mainly focuses on various tumors; its effect on BPD has yet to be
reported. The present study represents the first investigation of the
role and related mechanisms of the Twist1-Tie2-Angs signaling pathway in
hyperoxia-induced endothelial cell injury. Methods: Primary human
umbilical vein endothelial cells were used as an in vitro model. A
Twist1 inhibitor (harmine) was applied to normal and hyperoxia-exposed
endothelial cells. Then, we observed the permeability and tubule
formation ability of endothelial cells after reducing Twist1 protein.
Results: Hyperoxia increased the permeability of endothelial cells and
decreased tubule formation ability. Under physiological conditions
dominated by angiogenin 1 (Ang1), reducing the expression of Twist1
increases the permeability of endothelial cells and reduces tubule
formation ability. In contrast, under hyperoxia conditions dominated by
angiogenin 2 (Ang2), reducing the expression of Twist1 reduced the
permeability of endothelial cells and increased tubule formation
ability. Conclusion: Twist1 depends on the balance of Ang1 and Ang2 to
control the permeability and tubule formation of endothelial cells.
Reducing the levels of Twist1 may be a protective mechanism for BPD.