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Am J Physiol Lung Cell Mol Physiol (May 9, 2003). doi:10.1152/ajplung.00379.2002
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Submitted on November 5, 2002
Accepted on April 23, 2003

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

Brigham C. Willis1, Kwang-Jin Kim2, Xian Li2, Janice Liebler2, Edward D. Crandall2, and Zea Borok2*

1 Department of Anesthesiology Critical Care Medicine, Childrens Hospital Los Angeles, Los Angeles, CA, USA
2 Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: zborok{at}usc.edu.

Transforming growth factor-{beta}1 (TGF-{beta}1) may be a critical mediator of lung injury and subsequent remodeling during recovery. We evaluated the effects of TGF-{beta}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-{beta}1 (0.1-100 pM) from day 0 resulted in a concentration- and time-dependent 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 {alpha}1- and {beta}1-subunits were observed in TGF-{beta}1-treated monolayers. No change in the {alpha}-subunit of the rat epithelial sodium channel ({alpha}-rENaC) was seen. Exposure of confluent monolayers to TGF-{beta}1 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 TGF-{beta}1 modulates ion conductance and active transport characteristics of the alveolar epithelium, associated with increased Na+,K+-ATPase, but without a change in {alpha}-rENaC.




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