KERATINOCYTE GROWTH-FACTOR MODULATES ALVEOLAR EPITHELIAL-CELL PHENOTYPE IN-VITRO - EXPRESSION OF AQUAPORIN-5

We investigated the role of keratinocyte growth factor (KGF) in regula tion of alveolar epithelial cell (AEC) phenotype in vitro. Effects of KGF on cell morphology, expression of surfactant apoproteins A, B, and C (SP-A, -B, and -C), and expression of aquaporin 5 (AQP5), a water c hannel present in situ on the apical surface of alveolar type I (AT1) cells but not expressed in alveolar type II (AT2) cells, were evaluate d in AECs grown in primary culture. Observations were made on AEC mono layers grown in serum-free medium without KGF (control) or grown conti nuously in the presence of KGF (10 ng/ml) from either Day 0 (i.e., the time of plating) or Day 4 or 6 through Day 8 in culture. AECs monolay ers express AQP5 only on their apical surfaces as determined by cell s urface biotinylation studies. Control AECs grown in the absence of KGF through Day 8 express increasing levels of AQP5, consistent with tran sition toward the AT1 cell phenotype. Exposure of AECs to KGF from Day 0 results in decreased AQP5 expression, retention of a cuboidal morph ology, and greater numbers of lamellar bodies relative to control on D ay 8 in culture. AECs treated with KGF from Day 4 or 6 exhibit a decre ase in AQP5 expression through subsequent days in culture, as well as an increase in expression of surfactant apoproteins. These data, showi ng that KGF both prevents and reverses the increase in AQP5 (and decre ase in surfactant apoprotein) expression that accompanies progression of the AT2 toward the AT1 cell phenotype, support the concepts that tr ansdifferentiation between AT2 and AT1 cell phenotypes is at least par tially reversible and that KGF may play a major role in modulating AEC phenotype.