| First Author | Ruiz-Camp J | Year | 2019 |
| Journal | EMBO Mol Med | Volume | 11 |
| Issue | 3 | PubMed ID | 30770339 |
| Mgi Jnum | J:290538 | Mgi Id | MGI:6443900 |
| Doi | 10.15252/emmm.201809448 | Citation | Ruiz-Camp J, et al. (2019) Targeting miR-34a/Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia. EMBO Mol Med 11(3) |
| abstractText | 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)alpha-expressing myofibroblasts, a cell type critical for proper lung alveolarization. Global deletion of miR-34a; and inducible, conditional deletion of miR-34a in PDGFRalpha(+) 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 PDGFRalpha(+) 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. |
