Human epidermal growth factor receptor signaling in acute lung injury.
Acute lung injury (ALI) is a syndrome marked by increased permeability across the pulmonary epithelium resulting in pulmonary edema. Recent evidence suggests that members of the human epidermal growth factor receptor (HER) family are activated in alveolar epithelial cells during ALI and regulate alveolar epithelial barrier function. These tyrosine kinase receptors, which also participate in the pathophysiology of pulmonary epithelial malignancies, regulate cell growth, differentiation, and migration as well as cell-cell adhesion, all processes that influence epithelial injury and repair. In this review we outline mechanisms of epithelial injury and repair in ALI, activation patterns of this receptor family in pulmonary epithelial cells as a consequence injury, how receptor activation alters alveolar permeability, and the possible intracellular signaling pathways involved. Finally, we propose a theoretical model for how HER-mediated modulation of alveolar permeability might affect lung injury and repair. Understanding how these receptors signal has direct therapeutic implications in lung injury and other diseases characterized by altered epithelial barrier function.
Department of Medicine, National Jewish Health, 1400 Jackson Street, K736A, Denver, CO 80206, USA. FiniganJ@NJHealth.org
James H
JH
Finigan
Gregory P
GP
Downey
Jeffrey A
JA
Kern
D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D055371:Acute Lung Injury / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004815:Epidermal Growth Factor / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D010539:Permeability; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein