Abstract
Background
ALI/ARDS is a severe lung injury leading to refractory respiratory failure, accounting for high morbidity and mortality. However, therapeutic approaches are rather limited. Targeting long non-coding RNA MALAT1 and microRNA miR-181a-5p might be potential option for ALI/ARDS intervention.
Objective
We aimed to investigate the role of MALAT and miR-181a-5p in the pathogenesis of ALI/ARDS, and test the therapeutic effects of targeting MALAT and miR-181a-5p for ALI/ARDS intervention in vitro.
Methods
MALAT1 and miR-181a-5p levels were measured in plasma from ALI/ARDS patients. In vitro human pulmonary microvascular endothelial cell (HPMEC) injury was induced by LPS treatment, and molecular targets of MALAT1 and miR-181a-5p were explored by molecular biology approaches, mainly focusing on cell apoptosis and vascular inflammation. Interaction between MALAT1 and miR-181a-5p was also detected. Finally, the effects of targeting MALAT1 and miR-181a-5p for ALI/ARDS intervention were validated in a rat ALI/ARDS model.
Results
MALAT1 upregulation and miR-181a-5p downregulation were observed in ALI/ARDS patients. Transfection of mimic miR-181a-5p into HPMECs revealed decreased Fas and apoptosis, along with reduced inflammatory factors. Fas was proved to be a direct target of miR-181a-5p. Similar effects were also present upon MALAT1 knockdown. As for the interaction between MALAT1 and miR-181a-5p, MALAT1 knockdown increased miR-181a-5p expression. Knocking down of MALAT1 and miR-181a-5p could both improve the outcome in ALI/ARDS rats.
Conclusion
MALAT1 antagonism or miR-181a-5p could both be potential therapeutic strategies for ALI/ARDS. Mechanistically, miR-181a-5p directly inhibits Fas and apoptosis, along with reduced inflammation. MALAT1 negatively regulates miR-181a-5p.
Silencing of long non-coding RNA MEG3 alleviates lipopolysaccharide-induced acute lung injury by acting as a molecular sponge of microRNA-7b to modulate NLRP3