| First Author | Oak P | Year | 2017 |
| Journal | EMBO Mol Med | Volume | 9 |
| Issue | 11 | Pages | 1504-1520 |
| PubMed ID | 28923828 | Mgi Jnum | J:264661 |
| Mgi Id | MGI:6162000 | Doi | 10.15252/emmm.201607308 |
| Citation | Oak P, et al. (2017) Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease. EMBO Mol Med 9(11):1504-1520 |
| abstractText | 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-Ralpha gene in preterms with nCLD and directly test the effect of PDGF-Ralpha 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-Ralpha-dependent reduction in lung VEGF-A. TGF-beta contributes to the PDGF-Ralpha-dependent decrease in myofibroblast function. Remarkably, endotracheal treatment with exogenous PDGF-A rescues both the lung defects in haploinsufficient mice undergoing MV-O2 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-O2. |
