Lipoxin A 4 Attenuates Bronchopulmonary Dysplasia via Upregulation of Let-7c and Downregulation of TGF- β 1 Signaling Pathway

AbstractTransforming growth factor- β (TGF-β) superfamily members are key regulators for lung development and progress of bronchopulmonary dysplasia (BPD). The mechanisms by which lipoxin A4 (LXA4) attenuates development of BPD have not been clarified. Neonatal murine BPD models were inducted by hyperoxia treatment. Neonatal mice were exposed to room air or 85% O2 hyperoxia with or without treatment with 5S,6R-methyl-LXA4 or anti-TGF- β antibodies. Mouse lung epithelial cells (MLE-12 cells) and mouse embryonic fibroblasts (NIH/3T3 cells) were cultured in room air or 85% O2 followed by treatment of LXA4, anti-TGF- β antibodies, and let-7c mimic/anti-microRNA transfections. Treatment with 5S,6R-methyl-LXA4 and anti-TGF- β antibodies both attenuated the mice alveolar simplification induc...

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