Targeting miR-34a/ Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia

EMBO Mol Med. 2019 Mar;11(3):e9448. doi: 10.15252/emmm.201809448.


Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth characterized by arrested lung alveolarization, which generates lungs that are incompetent for effective gas exchange. We report here deregulated expression of miR-34a in a hyperoxia-based mouse model of BPD, where miR-34a expression was markedly increased in platelet-derived growth factor receptor (PDGFR)α-expressing myofibroblasts, a cell type critical for proper lung alveolarization. Global deletion of miR-34a; and inducible, conditional deletion of miR-34a in PDGFRα+ cells afforded partial protection to the developing lung against hyperoxia-induced perturbations to lung architecture. Pdgfra mRNA was identified as the relevant miR-34a target, and using a target site blocker in vivo, the miR-34a/Pdgfra interaction was validated as a causal actor in arrested lung development. An antimiR directed against miR-34a partially restored PDGFRα+ myofibroblast abundance and improved lung alveolarization in newborn mice in an experimental BPD model. We present here the first identification of a pathology-relevant microRNA/mRNA target interaction in aberrant lung alveolarization and highlight the translational potential of targeting the miR-34a/Pdgfra interaction to manage arrested lung development associated with preterm birth.

Keywords: bronchopulmonary dysplasia; hyperoxia; lung development; miR‐34a; platelet‐derived growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchopulmonary Dysplasia / metabolism*
  • Disease Models, Animal
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Hyperoxia / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Pulmonary Alveoli / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*


  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Receptor, Platelet-Derived Growth Factor alpha