EGAGenomicsCodelink Human Whole Genome Bioarrayhttps://ega-archive.org/datasets/EGAD0001000142411EGA dataset EGAD00010001424EGANeonatal 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 Acongenital chloride diarrhoea, familial chloride diarrhoea, familial chloride diarrhea, diarrhoea 1, Chloridorrhea, congenital, Darrow-gamble disease, chloride diarrhea, Finnish type, DRA, diarrhea 1, congenital chloride diarrhea, 2400010G15Rik, AW822050, congenital., CLD, cld, DIAR1, secretory chloride, Tmem112NEWBORN (0-27 DAYS), Neonatal, other disease, human disease, PDGFR binding, Drives, pulmo, platelet-derived growth factor, PDGF receptor binding, disorders, lung parenchyma, non-neoplastic, disease, pdgf, signalling process, pulmonary, diseases, parenchyma of lung, Diseases, lung, disease or disorder, Chronic, condition, disorder, Newborn, diseases and disorders, Homo sapiens disease, medical condition., Lungs, platelet-derived growth factor receptor ligand, PDGF, pdgf-a, attenuated, neoplasm, neoplasms, single organism signalingHuman, human being, whole genome, Man (Taxonomy), Homo sapiens, Man, Modern Man, human, Modern, whole blood.Materials, single-organism developmental process, Laboratory, postnatal development, Mus domesticus, septation, growth and development, CASP-14, House Mouse, PDGF A-chain protein, SUB, rat, diseases, DmelCG12298, parenchyma of lung, oxigeno, CG9063, SCRAMBLED, diseases and disorders, germacrene A synthase activity, division septum formation involved in mitotic cell cycle, cytopathology, pdgf-a, E948, GD-VEGF, PDGF1, KIF20A, septin assembly and septum biosynthesis, treatment, human disease, O, Oxygen-16, Swiss Mice, PDGF1 protein, BcDNA:GH03694, PDGF-AA, PA1, Oxygen, formation of barrier septum, [OO], C16orf53, Pathologies, septin assembly and septum formation involved in mitotic cell cycle, disease management, Therapies, barrier septum assembly involved in cell cycle cytokinesis, Homo sapiens disease, Vascular Endothelial Growth Factor-A, house mouse, DmelCG9063, single organism signaling, NEWBORN (0-27 DAYS), (+)-germacrene A synthase activity, Therapy, pulmo, aberrant, PDGFA protein, septin assembly and septum formation, STRUBBELIG, mouse, CASP14, lung parenchyma, platelet-derived growth factor alpha polypeptide, results, Glioma-Derived Vascular Endothelial Cell Growth Factor, PDGF-A, Sauerstoff, VEGF-A, Mini-ICE, Diseases, Genetic Materials, GAS, 6-trans-farnesyl-diphosphate diphosphate-lyase (germacrene-A-forming) activity, Genetic Material, neoplasms, CG12298., Mus musculus, platelet derived growth factor, Disauerstoff, dioxygen, endothelial cell apoptosis, histopathology, Caspase-14 subunit p10, mice, VPF, BcDNAGH03694, Swiss Mouse, INSDC_feature:gene, Caspase-14 subunit p19, MICE, division septum formation involved in cell cycle cytokinesis, Treatments, 3L6, human, domesticus, alpha protein, disease, rich, pulmonary, Material, Cistron, Mouse, platelet-derived growth factor receptor ligand, Vascular Endothelial Growth Factor, Glioma Derived Vascular Endothelial Cell Growth Factor, Vasculotropin, vegfa, Dioxygen, AT1G11140, 3.4.22.-, other disease, atypia, PDGFR binding, platelet-derived growth factor, number, E-948, 2-trans, Gene, mini-ICE, 8O, division septum assembly involved in cell cycle cytokinesis involved in mitotic cell cycle, CG12298, mitotic division septum assembly, Vascular Permeability Factor, dioxygene, House, Vascular, lung, disease or disorder, Mus musculus domesticus, atypical, Vascular permeability factor, vegf-a, Mice, attenuated, neoplasm, VEGF164, Permeability Factor, division septum assembly involved in cell cycle cytokinesis, Genetic, Swiss, mei-1794, PDGF A, barrier septum formation, non-neoplastic, disorder, SRF9, Pdgfa protein, molecular oxygen, Neonatal, Oxygen 16, PDGF AA, 6-trans-farnesyl-diphosphate diphosphate-lyase [(+)-germacrene-A-forming] activity, disorders, medical condition, defective, function, Haploinsufficiencies, (+)-(10R)-germacrene A synthase activity, Cistrons, oxygen, STRUBBELIG-RECEPTOR FAMILY 9, development, formation of division septum involved in mitotic cell cycle, Mus, condition, oxygene, OXYGEN MOLECULE, O2, septin assembly and septum biosynthesis involved in mitotic cell cycle, Vegf, Myofibroblast, PDGF-A protein, PDGF receptor binding, smooth muscle-like cell, Dub, postnatal growth, House Mice, Ventilations, barrier septum formation involved in cell cycle cytokinesis, Laboratory Mice, division septum formation involved in cell cycle cytokinesis involved in mitotic cell cycle, VEGF, pdgf, signalling process, Therapeutic, cardinality, Newborn, Treatment, Lungs, PDGF, biopsy, E 948, vegf, T19D16.8, growth, Laboratory Mouse, SCMfalseCodelink_HWG_CLD_BCodelink Human Whole Genome from Blood taken at 72 hours after birht2017-11-28 11:40:23EGAD00010001424960628923828EGAC00001000698EGAS00001002586