| First Author | Planès C | Year | 2010 |
| Journal | EMBO Mol Med | Volume | 2 |
| Issue | 1 | Pages | 26-37 |
| PubMed ID | 20043279 | Mgi Jnum | J:232314 |
| Mgi Id | MGI:5776471 | Doi | 10.1002/emmm.200900050 |
| Citation | Planes C, et al. (2010) ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1. EMBO Mol Med 2(1):26-37 |
| abstractText | Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance. |
