Modulation of ion conductance and active transport by TGF-β1 in alveolar epithelial cell monolayers

Transforming growth factor-beta1 (TGF-beta1) may be a critical mediator of lung injury and subsequent remodeling during recovery. We evaluated the effects of TGF-beta1 on the permeability and active ion transport properties of alveolar epithelial cell monolayers. Rat alveolar type II cells plated on polycarbonate filters in defined serum-free medium form confluent monolayers and acquire the phenotypic characteristics of alveolar type I cells. Exposure to TGF-beta1 (0.1 - 100 pM) from day 0 resulted in a concentration- and time-dependent decrease in transepithelial resistance (R-t) and increase in short-circuit current (I-sc). Apical amiloride or basolateral ouabain on day 6 inhibited Isc by 80 and 100%, respectively. Concurrent increases in expression of Na+- K+-ATPase alpha(1)- and beta(1)-subunits were observed in TGF-beta1-treated monolayers. No change in the alpha-subunit of the rat epithelial sodium channel (alpha-rENaC) was seen. Exposure of confluent monolayers to TGF-beta1 from day 4 resulted in an initial decrease in Rt within 6 h, followed by an increase in Isc over 72 - 96 h. These results demonstrate that TGF-beta1 modulates ion conductance and active transport characteristics of the alveolar epithelium, associated with increased Na+-K+-ATPase, but without a change in alpha-rENaC.