Targeting miR-34a

Autor: Jordi, Ruiz-Camp, Jennifer, Quantius, Ettore, Lignelli, Philipp F, Arndt, Francesco, Palumbo, Claudio, Nardiello, David E, Surate Solaligue, Elpidoforos, Sakkas, Ivana, Mižíková, José Alberto, Rodríguez-Castillo, István, Vadász, William D, Richardson, Katrin, Ahlbrecht, Susanne, Herold, Werner, Seeger, Rory E, Morty
Rok vydání: 2019
Předmět:
Zdroj: EMBO Molecular Medicine
ISSN: 1757-4684
Popis: 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.
Databáze: OpenAIRE
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