Late Breaking Abstract - The miR-34a/Pdgfra interaction can be targeted to correct defective alveolarization in experimental bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature neonates characterized by arrested lung alveolarization. MicroRNAs (miR) are poorly understood in the context of BPD. Here, a miR microarray on mouse lungs exposed to normoxia (21% O 2 ) or hyperoxia (85% O 2 ) revealed an up-regulation of the miR‑34a expression (at least 1.5-fold at all time-points) in mouse lungs maintained under hyperoxic conditions. Mice treated with an antagomiR-34a almost doubled the total number of alveoli (2.1 ± 0.4 × 10 6 ) and normalized the mean septal wall thickness (10.1 ± 2.3 µm) under hyperoxic conditions compared to the number of alveoli (1.2 ± 0.2 × 10 6 ) and septal wall thickness (17.8 ± 3.9 µm) assessed by stereology in mice injected with scrambled antagomiR (SCR). Platelet‑derived growth factor receptor (PDGFR)α, a target of miR‑34a, has been reported to be crucial for myofibroblast transdifferentiation and normal lung alveolarization. Isolated PDGFRα + cells by flow cytometry from mouse lungs exposed to 85% O 2 for the first five days of life revealed an up‑regulation of the miR-34a expression (3-fold). Mice injected with two target‑site blockers, to block the miR‑34a/ Pdgfra mRNA interaction, increased the total number of alveoli (1.7 ± 0.2 × 10 6 ) and normalized the septal wall thickness (11.6 ± 1.2 µm) under hyperoxic conditions compared to the number of alveoli (1.3 ± 0.1 × 10 6 ) and septal wall thickness (13.9 ± 1.4 µm) observed in SCR-treated mice. In conclusion, the inhibition of miR‑34a partially restored the total number of alveoli and normalised the septal wall thickness in mouse lungs maintained under hyperoxic conditions.