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Targeting miR-34a/ Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia.
- Source :
-
EMBO molecular medicine [EMBO Mol Med] 2019 Mar; Vol. 11 (3). - Publication Year :
- 2019
-
Abstract
- 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 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br /> (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
Details
- Language :
- English
- ISSN :
- 1757-4684
- Volume :
- 11
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- EMBO molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30770339
- Full Text :
- https://doi.org/10.15252/emmm.201809448