EGAGenomicsCodelink Human Whole Genome Bioarrayhttps://ega-archive.org/datasets/EGAD000100014259EGA dataset EGAD00010001425EGANeonatal 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 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.Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease.Oak Prajakta P, Pritzke Tina T, Thiel Isabella I, Koschlig Markus M, Mous Daphne S DS, Windhorst Anita A, Jain Noopur N, Eickelberg Oliver O, Foerster Kai K, Schulze Andreas A, Goepel Wolfgang W, Reicherzer Tobias T, Ehrhardt Harald H, Rottier Robbert J RJ, Ahnert Peter P, Gortner Ludwig L, Desai Tushar J TJ, Hilgendorff Anne AfalseCodelink_HWG_noCLD_CBCodelink Human Whole Genome from Blood taken at 72 hours after birht2017-11-26 20:50:51EGAD00010001425960628923828EGAC00001000698EGAS00001002586