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Oak, P. ; Pritzke, T. ; Thiel, I. ; Koschlig, M. ; Mous, D.S.* ; Windhorst, A.* ; Jain, N.* ; Eickelberg, O. ; Foerster, K.* ; Schulze, A.* ; Goepel, W.* ; Reicherzer, T.* ; Ehrhardt, H.* ; Rottier, R.J.* ; Ahnert, P.* ; Gortner, L.* ; Desai, T.J.* ; Hilgendorff, A.

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

EMBO Mol. Med. 9, 1504-1520 (2017)

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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

Corresponding Author

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

ISSN (print) / ISBN 1757-4676

e-ISSN 1757-4684

Journal EMBO Molecular Medicine

Quellenangaben Volume: 9, Issue: 11, Pages: 1504-1520

Publisher Wiley

Publishing Place Chichester

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Lung Health and Immunity (LHI)