Alveolar epithelial paxillin in postnatal lung alveolar development

TL;DR

Paxillin in lung cells helps develop alveoli in newborns by controlling surfactant production through specific signaling.

Contribution

This study identifies paxillin's role in postnatal lung development via CEBPA-ABCA3 signaling in alveolar epithelial cells.

Findings

Paxillin expression is higher in AT2 cells during the alveolar stage compared to the saccular stage.

Reduced paxillin in AT2 cells disrupts alveolar and vascular structures and lowers neonatal survival rates.

Paxillin modulates surfactant homeostasis by regulating ABCA3 and CEBPA in AT2 cells.

Abstract

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.

Summary: Epithelial cell paxillin is necessary for the postnatal lung alveolar development, which is mediated by CEBPA-ABCA3 signaling to control surfactant homeostasis.

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