The role of
cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in airway epithelial
wound repair was investigated using normal human bronchial epithelial (NHBE) cells and a human airway epithelial cell line (Calu-3) of serous gland origin. Measurements of
wound repair were performed using continuous impedance sensing to determine the time course for
wound closure. Control experiments showed that the increase in impedance corresponding to cell migration into the
wound was blocked by treatment with the actin polymerization inhibitor,
cytochalasin D. Time lapse imaging revealed that NHBE and Calu-3 cell
wound closure was dependent on cell migration, and that movement occurred as a collective sheet of cells. Selective inhibition of CFTR activity with
CFTR(inh)-172 or
short hairpin RNA silencing of CFTR expression produced a significant delay in
wound repair. The CF cell line UNCCF1T also exhibited significantly slower migration than comparable normal airway epithelial cells. Inhibition of CFTR-dependent
anion transport by treatment with
CFTR(inh)-172 slowed
wound closure to the same extent as silencing
CFTR protein expression, indicating that ion transport by CFTR plays a critical role in migration. Moreover, morphologic analysis of migrating cells revealed that CFTR inhibition or silencing significantly reduced lamellipodia protrusion. These findings support the conclusion that CFTR participates in airway epithelial
wound repair by a mechanism involving
anion transport that is coupled to the regulation of lamellipodia protrusion at the leading edge of the cell.