PDGF-A signaling is required for secondary alveolar septation and controls epithelial proliferation in the developing...

Platelet-derived growth factor A (PDGF-A) signaling through PDGF receptor α is essential for alveogenesis. Previous studies have shown that Pdgfa mouse lungs have enlarged alveolar airspace with absence of secondary septation, both distinctive features of bronchopulmonary dysplasia. To study how PDGF-A signaling is involved in alveogenesis, we generated lung-specific Pdgfa knockout mice (Pdgfa) and characterized their phenotype postnatally. Histological differences between mutant mice and littermate controls were visible after the onset of alveogenesis and maintained until adulthood. Additionally, we generated Pdgfa mice in which Pdgfra⁺ cells exhibit nuclear GFP expression. In the absence of PDGF-A, the number of Pdgfra cells was significantly decreased. In addition, proliferation of Pdgfra cells was reduced. During alveogenesis, Pdgfra myofibroblasts failed to form the α-smooth muscle actin rings necessary for alveolar secondary septation. These results indicate that PDGF-A signaling is involved in myofibroblast proliferation and migration. In addition, we show an increase in both the number and proliferation of alveolar type II cells in Pdgfa lungs, suggesting that the increased alveolar airspace is not caused solely by deficient myofibroblast function.