| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Division of Pulmonary, Allergy, and Critical Care Medicine, 2Department of Pediatrics, 3Department of Cell Biology and Physiology, and 4Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 20 October 2007 ; accepted in final form 25 February 2008
Airway surface liquid (ASL) absorption is initiated by Na+ entry via epithelial Na+ channels (ENaC), which establishes an osmotic gradient that drives fluid from the luminal to serosal airway surface. We and others have recently reported that a protease/anti-protease balance regulates ENaC in human airway epithelial cells (HAEC) and provides a mechanism for autoregulation of ASL volume. In cystic fibrosis (CF), this balance is disturbed, leading to constitutive proteolytic activation of ENaC and the pathological Na+ hyperabsorption characteristic of this airway disease. Prostasin is a glycosylphosphatidylinositol-anchored serine protease that activates ENaC and is expressed on the surface epithelium lining the airway. In this report we present evidence that prostasin expression is regulated by the ASL volume, allowing for increased proteolytic activation of ENaC when the ASL volume is high. Prostasin activity is further regulated by the cognate serpin protease nexin-1 (PN-1), which is expressed in HAEC and inhibits Na+ absorption by forming an inactive complex with prostasin and preventing the proteolytic processing of prostasin. Whereas these mechanisms regulate prostasin expression in response to ASL volume in non-CF epithelia, HAEC cultured from CF patients express >50% more prostasin on the epithelial surface. These findings suggest that a proteolytic cascade involving prostasin, an upstream prostasin-activating protease, and PN-1 regulate Na+ absorption in the airway and that abnormal prostasin expression contributes to excessive proteolytic activation of ENaC in CF patients.
epithelial sodium channels; protease nexin 1; bronchial epithelial cultures; matriptase
This article has been cited by other articles:
|
|
 |
|
  Y. Song, W. Namkung, D. W. Nielson, J.-W. Lee, W. E. Finkbeiner, and A. S. Verkman Airway surface liquid depth measured in ex vivo fragments of pig and human trachea: dependence on Na+ and Cl- channel function Am J Physiol Lung Cell Mol Physiol, December 1, 2009; 297(6): L1131 - L1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lazrak, I. Nita, D. Subramaniyam, S. Wei, W. Song, H.-L. Ji, S. Janciauskiene, and S. Matalon {alpha}1-Antitrypsin Inhibits Epithelial Na+ Transport In Vitro and In Vivo Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 261 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garcia-Caballero, J. E. Rasmussen, E. Gaillard, M. J. Watson, J. C. Olsen, S. H. Donaldson, M. J. Stutts, and R. Tarran SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage PNAS, July 7, 2009; 106(27): 11412 - 11417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Coote, H. C. Atherton-Watson, R. Sugar, A. Young, A. MacKenzie-Beevor, M. Gosling, G. Bhalay, G. Bloomfield, A. Dunstan, R. J. Bridges, et al. Camostat Attenuates Airway Epithelial Sodium Channel Function in Vivo through the Inhibition of a Channel-Activating Protease J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 764 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tarran Raising the volume on near-silent epithelial Na+ channels J. Physiol., October 1, 2008; 586(19): 4583 - 4584. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
