Modulation of Ion Conductance and Active Transport by Tgf- 1 in Alveolar Epithelial Cell Monolayers

Transforming growth factor1 (TGF1) may be a critical mediator of lung injury and subsequent remodeling during recovery. We evaluated the effects of TGF1 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 TGF1 (0.1-100 pM) from day 0 resulted in a concentrationand timedependent decrease in transepithelial resistance (Rt) and increase in short circuit current (Isc). Apical amiloride or basolateral ouabain on day 6 inhibited Isc by 80% and 100%, respectively. Concurrent increases in expression of Na,K-ATPase 1and 1-subunits were observed in TGF1-treated monolayers. No change in the -subunit of the rat epithelial sodium channel ( -rENaC) was seen. Exposure of confluent monolayers to TGF1 from day 4 resulted in an initial decrease in Rt within 6 hours, followed by an increase in Isc over 72-96 hours. These results demonstrate that TGF1 modulates ion conductance and active transport characteristics of the alveolar epithelium, associated with increased Na,K-ATPase, but without a change in -rENaC.