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EDITORIAL FOCUS

Modulation of ion conductance and active transport by TGF-1 in alveolar epithelial cell monolayers

¹Department of Anesthesiology Critical Care Medicine, Childrens Hospital, Los Angeles, and ²Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033

Submitted 5 November 2002 ; accepted in final form 23 April 2003

Transforming growth factor-1 (TGF-1) may be a critical mediator of lung injury and subsequent remodeling during recovery. We evaluated the effects of TGF-1 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-1 (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 I_sc by 80 and 100%, respectively. Concurrent increases in expression of Na⁺-K⁺-ATPase ₁- and ₁-subunits were observed in TGF-1-treated monolayers. No change in the -subunit of the rat epithelial sodium channel (-rENaC) was seen. Exposure of confluent monolayers to TGF-1 from day 4 resulted in an initial decrease in R_t within 6 h, followed by an increase in I_sc over 72-96 h. These results demonstrate that TGF-1 modulates ion conductance and active transport characteristics of the alveolar epithelium, associated with increased Na⁺-K⁺-ATPase, but without a change in -rENaC.

transforming growth factor; alveolar epithelium; alveolar epithelial cells; epithelial sodium channel; sodium pump; acute lung injury

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