Epidermal growth factor receptor (EGFR) contributes to fetal lung fibroblast injury induced by mechanical stretch

Epidermal growth factor receptor (EGFR) is critical for normal fetal lung development. However, the role of this receptor in lung injury induced by mechanical ventilation is controversial.

To investigate in vitro whether EGFR plays a protective role or contributes to stretch-induced lung injury.

Fetal lung fibroblasts were isolated from wild-type and EGFR knockout mice and exposed to physiologic stretch (2.5% elongation) or injurious stretch (20% distention). Cells were evaluated for necrosis, apoptosis, proliferation and inflammation.

Injurious stretch increased lactate dehydrogenase (LDH) release to similar degree in wild-type and knockout cells. In contrast, 20% stretch increased cleaved caspase-3 and decreased proliferating cell nuclear antigen (PCNA) only in wild-type cells. Furthermore, 20% stretch increased macrophage inflammatory protein-2 (MIP-2) and monocyte chemotactic protein-1 (MCP-1) by 3-5 fold in wild-type cells. In contrast, in knockout cells MIP-2 decreased by 50% and MCP-1 only increased by 60% when compared to physiologic stretch.

Our data show a decrease of apoptosis and inflammation and absence of decreased proliferation after injurious stretch of fetal fibroblasts lacking EGFR. These data suggest that EGFR contributes to lung injury mediated by stretch. We speculate that EGFR may contribute to the arrest of lung development observed after mechanical ventilation by decreasing the population of lung fibroblasts.