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

EMBO Mol. Med. 9, 1504-1520 (2017)
Publishers Version Research data DOI PMC
Open Access Gold
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as soon as is submitted to ZB.
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 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Pdgf‐rα ; Vegf‐a ; Bronchopulmonary Dysplasia ; Neonatal Chronic Lung Disease ; Transforming Growth Factor‐β; Growth-factor Receptor; Newborn Rat Lung; Bronchopulmonary Dysplasia; Mechanical Ventilation; Pulmonary Inflammation; Preterm Infants; Expression; Mice; Alpha; Fibroblasts
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