Na1-K1-ATPase expression in alveolar epithelial cells: upregulation of active ion transport by KGF

Borok, Zea, Spencer I. Danto, Luis L. Dimen, XiaoLing Zhang, and Richard L. Lubman. Na1-K1-ATPase expression in alveolar epithelial cells: upregulation of active ion transport by KGF. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L149–L158, 1998.—We evaluated the effects of keratinocyte growth factor (KGF) on alveolar epithelial cell (AEC) active ion transport and on rat epithelial Na channel (rENaC) subunit and Na1-K1-adenosinetriphosphatase (ATPase) subunit isoform expression using monolayers of AEC grown in primary culture. Rat alveolar type II cells were plated on polycarbonate filters in serum-free medium, and KGF (10 ng/ml) was added to confluent AEC monolayers on day 4 in culture. Exposure of AEC monolayers to KGF on day 4 resulted in dose-dependent increases in short-circuit current (Isc) compared with controls by day 5, with further increases occurring through day 8. Relative Na1-K1-ATPase a1-subunit mRNA abundance was increased by 41% on days 6 and 8 after exposure to KGF, whereas a2-subunit mRNA remained only marginally detectable in both the absence and presence of KGF. Levels of mRNA for the b1-subunit of Na1-K1-ATPase did not increase, whereas cellular a1and b1-subunit protein increased 70 and 31%, respectively, on day 6. mRNA for a-, b-, and g-rENaC all decreased in abundance after treatment with KGF. These results indicate that KGF upregulates active ion transport across AEC monolayers via a KGF-induced increase in Na pumps, primarily due to increased Na1-K1-ATPase a1-subunit mRNA expression. We conclude that KGF may enhance alveolar fluid clearance after acute lung injury by upregulating Na pump expression and transepithelial Na transport across the alveolar epithelium.