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.

Bronchopulmonary dysplasia is a relatively common and severe complication of prematurity, and its pathogenesis remains ambiguous. Revolutionary advances in microbiological analysis techniques, together with the growing sophistication of the gut-lung axis hypothesis, have resulted in more studies linking gut microbiota dysbiosis to the occurrence and development of bronchopulmonary dysplasia. The present article builds on current findings to examine the intrinsic associations between gut microbiota and bronchopulmonary dysplasia. The gut microbiota affects bronchopulmonary dysplasia via several potential mechanisms including alteration of the gut-lung axis, promotion of inflammation and the ensuing growth effects, therefore these are also investigated. By evaluating the potential mechanisms, new therapeutic targets and potential therapeutic modalities for BPD can be identified from a microecological perspective.