A breath of fresh air in lung regeneration

Abstract

Enhancing the ability of the lungs to regenerate following injury could revolutionize the treatment of a wide range of different diseases. In this issue, Kumar et al. (2011) and Ding et al. (2011) dissect the cellular and molecular mechanisms of murine lung regeneration following injury and provide insights into the basic biology of the organ with implications for development of future therapeutic approaches.

Figure 1. Lung Regeneration in Response to Reduction in Pulmonary Function

(A) Alveolar epithelium regeneration after infection with influenza A virus starts with the appearance of p63⁺ Krt5⁺ basal cells in the bronchial epithelium, clonal expansion of basal cells into the peribronchiolar space, and their organization and differentiation into alveolar epithelial cells. dpi, days postinfection. (B) Compensatory lung growth following unilateral pneumonectomy occurs predominantly at the level of the alveolar sac, where pulmonary endothelial and alveolar epithelial cells are in close proximity. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling cascades that originate in the pulmonary endothelial cell induce expression of matrix metalloproteinase 14 (MMP14). MMP14 generates EGF-like ligands, including heparin binding EGF-like growth factor (HB-EGF) and EGF-like fragment of laminin5 γ2, which activate EGF receptor (EGFR) on the alveolar epithelial cell, driving it to proliferate.