| First Author | Gouveia L | Year | 2018 |
| Journal | Development | Volume | 145 |
| Issue | 7 | PubMed ID | 29636361 |
| Mgi Jnum | J:264108 | Mgi Id | MGI:6191984 |
| Doi | 10.1242/dev.161976 | Citation | Gouveia L, et al. (2018) PDGF-A signaling is required for secondary alveolar septation and controls epithelial proliferation in the developing lung. Development 145(7):dev161976 |
| abstractText | Platelet-derived growth factor A (PDGF-A) signaling through PDGF receptor alpha 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(fl/-); Spc-cre) 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(fl/-); Spc-cre; Pdgfra(GFP/+) mice in which Pdgfra(+) cells exhibit nuclear GFP expression. In the absence of PDGF-A, the number of Pdgfra(GFP+) cells was significantly decreased. In addition, proliferation of Pdgfra(GFP+) cells was reduced. During alveogenesis, Pdgfra(GFP+) myofibroblasts failed to form the alpha-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(fl/-); Spc-cre lungs, suggesting that the increased alveolar airspace is not caused solely by deficient myofibroblast function. |
