Back to Search Start Over

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

Authors :
Ruiz-Camp J
Quantius J
Lignelli E
Arndt PF
Palumbo F
Nardiello C
Surate Solaligue DE
Sakkas E
Mižíková I
Rodríguez-Castillo JA
Vadász I
Richardson WD
Ahlbrecht K
Herold S
Seeger W
Morty RE
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