Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease.

ABSTRACT: Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O₂). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O₂ In the context of MV-O₂, attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A. TGF-β contributes to the PDGF-Rα-dependent decrease in myofibroblast function. Remarkably, endotracheal treatment with exogenous PDGF-A rescues both

SUBMITTER: Oak P 

PROVIDER: S-EPMC5666314 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature