The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is the most common challenge in preterm neonates. Retardation of alveolar development characterizes the pulmonary pathology in BPD. In the present study, we explored the roles of the CD146-HIF-1α axis in BPD. We demonstrated that the levels of reactive oxygen species (ROS) and soluble CD146 (sCD1146) were increased in the peripheral blood of preterm neonates with BPD. In alveolar epithelial cells, hyperoxia promoted the expression of HIF-1α and CD146, which reinforced each other. In a mouse model of BPD, by exposing pups to 65% hyperoxia, HIF-1α and CD146 were increased in the pulmonary tissues. Mechanistically, CD146 hindered the migration of alveolar epithelial cells; in contrast, movement was significantly enhanced in CD146-knockout alveolar epithelial cells. As expected, CD146-knockout ameliorated alveolarization and improved BPD disease severity. Taken together, our findings imply that the CD146-HIF-1α axis contributes to alveolarization and that CD146 may be a novel candidate in BPD therapy.

Tat-P combined with GAPR1 releases Beclin1 to promote autophagy and improve Bronchopulmonary dysplasia model

“… 5 , 17 Repairing alveolar epithelial cells is vital for treating lung injury associated with BPD and has been extensively studied to elucidate the molecular mechanisms underlying BPD. 10 , 18 , 19 In our study, we observed that Tat-P readily entered alveolar epithelial cells promoting autophagy and reversing the autophagy inhibition caused by hyperoxia. This suggests that Tat-P induces autophagy in alveolar epithelial cells and promotes cellular repair, which has implications for preventing and treating BPD.…”

Tenascin-C modulates alveolarization in bronchopulmonary dysplasia

“…As previously mentioned, cultured lung alveolar cells only express very little total TN-C [ 40 ]. We previously reported that HIF-1α mediates the migration of alveolar epithelial cells and participates in the progression of BPD [ 41 ]. In the present study, we demonstrated that pulmonary epithelial cells could release more soluble TN-C in response to hyperoxia, a phenomenon that could be connected to the HIF-1α pathway.…”

Emerging role of metabolic reprogramming in hyperoxia-associated neonatal diseases

“…Although HIF-1α is necessary for lung development, excessive HIF-1α can have counterproductive effects. Animal studies have demonstrated increased HIF-1α levels in BPD models [ 96 ]. Furthermore, mtROS can activate NOX1 in BPD mice [ 97 ].…”