PDGF-Ralpha gene expression predicts proliferation, but PDGF-A suppresses transdifferentiation of neonatal mouse lung myofibroblasts.

Background: Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Ralpha, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because pdgfa-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Ralpha correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (alphaSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects alphaSMA or modifies stimulation by transforming growth factor beta (TGFbeta).

Platelet-derived growth factor receptor-alpha-expressing cells localize to the alveolar entry ring and have characteristics of myofibroblasts during pulmonary alveolar septal formation.

Platelet-derived growth factor-A and its receptor, platelet-derived growth factor receptor-alpha (PDGF-Ralpha), are required for formation of the secondary pulmonary alveolar septa in mice. However, it remains unclear how these molecules direct the secondary septation process. We have examined the abundance, location, and the accumulation of alpha-smooth muscle actin (alphaSMA), neutral lipid droplets, and elastin in the proximity of PDGF-Ralpha-expressing alveolar cells during postnatal days 4 through 12 in the mouse.