Open AccessTargeting miR‐34a/ Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia
Author(s) -
RuizCamp Jordi,
Quantius Jennifer,
Lignelli Ettore,
Arndt Philipp F,
Palumbo Francesco,
Nardiello Claudio,
Surate Solaligue David E,
Sakkas Elpidoforos,
Mižíková Ivana,
RodríguezCastillo José Alberto,
Vadász István,
Richardson William D,
Ahlbrecht Katrin,
Herold Susanne,
Seeger Werner,
Morty Rory E
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809448
Subject(s) - bronchopulmonary dysplasia , pdgfra , cancer research , medicine , biology , genetics , pregnancy , stromal cell , gestational age , gist
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 PDGFR α + 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 PDGFR α + myofibroblast abundance and improved lung alveolarization in newborn mice in an experimental BPD model. We present here the first identification of a pathology‐relevant micro RNA / 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.