Alveolar epithelial paxillin in postnatal lung alveolar development.

Focal adhesion protein, paxillin plays an important role in embryonic development. We have reported that paxillin controls directional cell motility and angiogenesis. The role of paxillin in lung development remains unclear. Paxillin expression is higher in mouse pulmonary alveolar epithelial type 2 (AT2) cells at postnatal day (P)10 (alveolar stage) compared to P0 (saccular stage). The alveolar and vascular structures are disrupted, lung compliance is reduced, and the postnatal survival rate is lower in tamoxifen-induced PxniΔAT2 neonatal mice, in which the levels of paxillin in AT2 cells are knocked down. Surfactant protein expression and lamellar body structure are also inhibited in PxniΔAT2 neonatal mouse lungs. The expression of lipid transporter ABCA3 and its transcriptional regulator CEBPA that control surfactant homeostasis is inhibited in PxniΔAT2 neonatal mouse AT2 cells. These findings suggest that paxillin controls lung alveolar development through CEBPA-ABCA3 signaling in AT2 cells. Modulation of paxillin in AT2 cells may be novel interventions for neonatal lung developmental disorder.