title: Epidermal growth factor receptor (EGFR) contributes to fetal lung fibroblast injury induced by mechanical stretch.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To investigate in vitro whether EGFR plays a protective role or contributes to stretch-induced lung injury.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Women & Infants Hospital of Rhode Island and the Warren Alpert Medical School of Brown University , Providence, Rhode Island , USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Giordani
authors.forename: Christina M
authors.initials: CM
authors.lastname: DeBenedictus
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Esteban
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D047109:Fetal Development; D005347:Fibroblasts / Q000473:pathology; D008168:Lung / Q000254:growth & development*; D055370:Lung Injury / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D066246:ErbB Receptors