NA-K+-ATPASE EXPRESSION IN ALVEOLAR EPITHELIAL-CELLS - UP-REGULATION OF ACTIVE ION-TRANSPORT BY KGF()

We evaluated the effects of keratinocyte growth factor (KGF) on alveol ar epithelial cell (AEC) active ion transport and on rat epithelial Na channel (rENaC) subunit and Na+-K+-adenosinetriphosphatase (ATPase) s ubunit isoform expression using monolayers of AEC grown in primary cul ture. Rat alveolar type II cells were plated on polycarbonate filters in serum-free medium, and KGF (10 ng/ml) was added to confluent AEC mo nolayers on day 4 in culture. Exposure of AEC monolayers to KGF on day 4 resulted in dose-dependent increases in short-circuit current (I-sc ) compared with controls by day 5, with further increases occurring th rough day 8. Relative Na+-K+-ATPase alpha(1)-subunit mRNA abundance wa s increased by 41% on days 6 and 8 after exposure to KGF, whereas alph a(2)-subunit mRNA remained only marginally detectable in both the abse nce and presence of KGF. Levels of mRNA for the beta(1)-subunit of Na-K+-ATPase did not increase, whereas cellular alpha(1)- and beta(1)-su bunit protein increased 70 and 31%, respectively, on day 6. mRNA for a lpha-, beta-, and gamma-rENaC all decreased in abundance after treatme nt with KGF. These results indicate that KGF upregulates active ion tr ansport across AEC monolayers via a KGF-induced increase in Na pumps, primarily due to increased Ma(+)-K+-ATPase alpha(1)-subunit mRNA expre ssion. We conclude that KGF may enhance alveolar fluid clearance after acute lung injury by upregulating Na pump expression and transepithel ial Na transport across the alveolar epithelium.