Modulation of ion conductance and active transport by TGF-beta 1 in alveolar epithelial cell monolayers.
Transforming growth factor-beta1 (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 h, followed by an increase in Isc over 72-96 h. 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.
Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, California 90033, USA.
Brigham C
BC
Willis
Kwang-Jin
KJ
Kim
Xian
X
Li
Janice
J
Liebler
Edward D
ED
Crandall
Zea
Z
Borok
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D004232:Diuretics / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D005455:Fluorescent Antibody Technique; D008171:Lung Diseases / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D004232:Diuretics; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D010042:Ouabain; D000584:Amiloride; D000254:Sodium-Potassium-Exchanging ATPase