Work

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

Year: 2017

Type: article

Abstract: Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O 2 ).Regardless, the primary molecular driver of the disease remains elusive.We discover significant enrichment for SNPs in the PDGF-Ra gene in preterms with nCLD and directly test the effect of PDGF-Ra haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O 2 .In the context of MV-O 2 , attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Ra-dependent reduction in lung VEGF-A.TGF-b contributes to the PDGF-Ra-dependent decrease in myofibroblast function.Remarkably, endotracheal treatment with exogenous PDGF-A rescues both the lung defects in haploinsufficient mice undergoing MV-O 2 .Overall, our results establish attenuated PDGF signaling as an important driver of nCLD pathology with provision of PDGF-A as a protective strategy for newborns undergoing MV-O 2 .

Source: EMBO Molecular Medicine

DOI: 10.15252/emmm.201607308