Damage to the airway epithelium occurs due to trauma during mechanical ventilation and in inflammatory diseases such as asthma. Rapid repair of the epithelium is critical for maintaining barrier function. The repair process must take place as the epithelium undergoes cyclic strain during respiration. We used an in vitro model of wound closure to examine the roles of cyclic strain and keratinocyte growth factor (KGF) in airway epithelium. Human and cat tracheal epithelial cells were grown on Silastic membranes and subjected to cyclic strain using the Flexercell apparatus. We demonstrated that both cyclic elongation and compression (30 cycles/min) inhibit wound closure compared with static controls. KGF accelerated wound closure in all monolayers and overcame the inhibitory effect of cyclic strain. Since wound closure occurs by cell spreading, migration, and proliferation, we measured cell area (spreading) and cell velocity (migration) before proliferation would occur. After 12 hr in static cultures, KGF stimulated migration (from 16.8±0.9 to 25.1±0.6 μm/hr) but had no effect on spreading. In cyclically stretched monolayers, cell velocity was 11.1±0.6 and 13.7±0.9 in the compressed and stretched regions, respectively. KGF increased cell velocity to 24.1±0.7 and 22.2±0.9, respectively. Also, KGF inhibited the decrease in cell area caused by cyclic compression. KGF enhances wound repair by stimulating cell migration and overcomes the inhibition of cell spreading caused by cyclic compression.
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology