Remodeling in the Developing Lung – Role for the EGF Receptor

The alveolar phase of lung development occurs predominantly after birth in humans and rodents. Studies in animal models have shown that insults that impact hormonal and growth factor signaling in the neonatal lung can disrupt morphogenesis and cause alterations in lung structure and function that persist into adulthood. Clinical data in humans that exemplify this include children with bronchopulmonary dysplasia (BPD) and asthma. Long‐term outcome studies have suggested that even infants with mild BPD, or who recover from BPD, may be at increased risk for asthma and chronic obstructive pulmonary disease later in life. Children with asthma have a more rapid decline in lung function as they age compared to normal individuals. While the pathogenesis is unclear, lung remodeling is thought to play an important role in declining lung function in these diseases. Clinical studies have associated increases in the EGF receptor (EGFR) and its ligands, including TGF‐α, with lung remodeling in pediatric and adult lung diseases, including BPD and asthma. Work from our group has shown that elevated EGFR signaling in lung specific TGF‐α transgenic mice can disrupt pre‐ and postnatal lung morphogenesis and cause fibrosis and remodeling. Even transient increases in EGFR signaling during the alveolar phase disrupted lung morphogenesis and caused chronic lung disease.