Effect of Slit/Robo signaling on regeneration in lung emphysema

Abstract

Emphysema: Can lung cells regenerate? A protein called Slit2 may help in treating emphysema by promoting regeneration of cells that line the tiny air sacs called alveoli in the lungs. In the alveoli, oxygen is transferred from the lungs to the blood. In emphysema, the alveoli become damaged, reducing patients' ability to exhale 'old' air and limiting capacity to breathe in fresh, oxygen-rich air. No treatments are available. Yeon-Mok Oh at the University of Ulan College of Medicine, Seoul, South Korea and co-workers investigated whether Slit2, known to be involved in nervous system development, cell proliferation, and migration, could aid in regenerating lung cells. Testing in mouse lung cells produced increased proliferation and migration. Further testing in a mouse model of emphysema showed that the alveoli could regenerate. These results hold promise for developing new treatments for emphysema.

Emphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.