Abstract
OBJECTIVE: We aimed to explore the level of PS, cell viability, inflammatory factors, and apoptosis in neonatal respiratory distress syndrome (ARDS). Besides, we explored the potential relationship between ACE2, SIRT1/eNOS pathway, and hypoxia-induced AT II cell damage. METHODS: The hUC-MSC-derived AT II cells were verified by IF and ICC, whereas qRT-PCR was used for PS and AT II cell marker (CK-8 and KGF). The AT II cell damage model was established by hypoxia exposure. The enhanced expression of ACE2 was tested after transfection with pcDNA3.1-ACE2 by western blot. The effects of hypoxia and ACE2 on AT II cells were evaluated by MTT, western blot, ELISA, and flow cytometry. The involvement of the SIRT1/eNOS pathway in AT II cell's protective functions against NRDS was verified with the addition of SIRT1 inhibitor EX527. RESULTS: Based on the successful differentiation of AT II cells from hUC-MSCs and the buildup of AT II cell damage model, the overexpressed ACE2 impeded the hypoxia-induced cellular damage of AT II cells. It also counteracted the inhibitory effects of hypoxia on the secretion of PS. Overexpression of ACE2 rescued the cell viability and suppressed the secretion of inflammatory cytokines and the apoptosis of AT II cells triggered by hypoxia. And ACE2 activated the SIRT1/eNOS pathway to play its cell-protective and anti-inflammatory roles. CONCLUSION: Our findings provided information that ACE2 prevented AT II cells from inflammatory damage through activating the SIRT1/eNOS pathway, which suggested that ACE2 might become a novel protective agent applied in the protection and treatment of NRDS.