Secondary crest myofibroblast PDGFRα controls the elastogenesis pathway via a secondary tier of signaling networks during alveologenesis

• DOI: 10.1242/dev.176354
• Publication Date: 2019-07-22T15:05:12Z
• Authors: Changgong Li; Matt K. Lee; Feng Gao; Sha Webster; Helen Di; Jiang Duan; Chang-Yo Yang; Navin Bhopal; Neil Peinado; Gloria Pryhuber; Susan M. Smith; Zea Borok; Saverio Bellusci; Parviz Minoo
• Keywords: PDGFRA; Myofibroblast

ABSTRACT Postnatal alveolar formation is the most important and least understood phase of lung development. Alveolar pathologies are prominent in neonatal adult diseases. The mechanisms alveologenesis remain largely unknown. We inactivated Pdgfra postnatally secondary crest myofibroblasts (SCMF), a subpopulation mesenchymal cells. Lack arrested akin to bronchopulmonary dysplasia (BPD), chronic disease. transcriptome mutant SCMF revealed 1808 altered genes encoding transcription factors, signaling extracellular matrix molecules. Elastin mRNA was reduced, its distribution abnormal. Absence disrupted expression elastogenic genes, including members Lox, Fbn Fbln families. Expression EGF family increased when Tgfb1 repressed mouse. Similar, but not identical, results were found human BPD samples. In vitro, blocking PDGF decreased gene associated with Egf Tgfb mRNAs. effect reversible by inhibiting or activating TGFβ signaling. These observations demonstrate previously unappreciated postnatal role PDGFA/PDGFRα controlling via tier networks composed TGFβ.