Inhibition of CLC-2 chloride channel expression interrupts expansion of fetal lung cysts.
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| Abstract |
Normal lung morphogenesis is dependent on chloride-driven fluid transport. The molecular identity of essential fetal lung chloride channel(s) has not been elucidated. CLC-2 is a chloride channel, which is expressed on the apical surface of the developing respiratory epithelium. CLC-2-like pH-dependent chloride secretion exists in fetal airway cells. We used a 14-day fetal rat lung submersion culture model to examine the role of CLC-2 in lung development. In this model, the excised fetal lung continues to grow, secrete fluid, and become progressively cystic in morphology (26). We inhibited CLC-2 expression in these explants, using antisense oligonucleotides, and found that lung cyst morphology was disrupted. In addition, transepithelial voltage (V(t)) of lung explants transfected with antisense CLC-2 was inhibited with V(t) = -1.5 +/- 0.2 mV (means + SE) compared with -3.7 +/- 0.3 mV (means + SE) for mock-transfected controls and -3.3 +/- 0.3 mV (means + SE) for nonsense oligodeoxynucleotide-transfected controls. This suggests that CLC-2 is important for fetal lung fluid production and that it may play a role in normal lung morphogenesis.
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| Authors | Carol J Blaisdell, Marcelo M Morales, Ana Carolina Oliveira Andrade, Penelope Bamford, Michael Wasicko, Paul Welling |
| Journal | American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 286 Issue 2 Pg. L420-6 (Feb 2004) ISSN: 1040-0605 [Print] United States |
| PMID | 14711803 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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