Inhibition of protease-epithelial sodium channel signaling improves mucociliary function in cystic fibrosis airways

American Journal of Respiratory and Critical Care Medicine

Volumn 194, Issue 6, 2016, Pages 701-710

  Reihill, James A ^a   Walker, Brian ^a   Hamilton, Robert A ^a   Ferguson, Timothy E G ^a   Elborn, J Stuart ^b   Stutts, M Jackson ^c   Harvey, Brian J ^d   Saint Criq, Vinciane ^d   Hendrick, Siobhan M ^d   Martin, S Lorraine ^a  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^b QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^c UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^d BEAUMONT HOSPITAL   (Ireland)

Author keywords

Airway surface liquid; Channel activating proteases; Furin; Prostasin; Pseudomonas aeruginosa exotoxin A

Indexed keywords

EPITHELIAL SODIUM CHANNEL; EPITHELIAL SODIUM CHANNEL BLOCKING AGENT; FURIN; LACTATE DEHYDROGENASE; MATRIPTASE; PROSTASIN; PROTEINASE; QUB TL1; SODIUM; UNCLASSIFIED DRUG; ARGININE; HUMAN AIRWAY TRYPSIN-LIKE PROTEASE; PHOSPHONIC ACID DERIVATIVE; QUB-TL1 COMPOUND; SERINE PROTEINASE; SODIUM CHANNEL; SODIUM CHANNEL BLOCKING AGENT;

AIRWAY EPITHELIAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL FUNCTION; CELL SURFACE; CONFOCAL MICROSCOPY; CYTOTOXICITY; DRUG SYNTHESIS; ENZYME ACTIVATION; HUMAN; HUMAN CELL; INTERNALIZATION; LUNG FIBROSIS; MUCOCILIARY CLEARANCE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PSEUDOMONAS AERUGINOSA; SIGNAL TRANSDUCTION; SODIUM ABSORPTION; SURFACE PROPERTY; ANALOGS AND DERIVATIVES; CELL CULTURE; CYSTIC FIBROSIS; CYTOLOGY; DRUG EFFECTS; PHYSIOLOGY; RESPIRATORY MUCOSA;

ARGININE; CELLS, CULTURED; CYSTIC FIBROSIS; HUMANS; MUCOCILIARY CLEARANCE; ORGANOPHOSPHONATES; RESPIRATORY MUCOSA; SERINE ENDOPEPTIDASES; SODIUM CHANNEL BLOCKERS; SODIUM CHANNELS;

EID: 84988921360     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201511-2216OC     Document Type: Article

References (56)

1. Davies JC, Alton EW, Bush A. Cystic fibrosis. BMJ 2007;335:1255-1259
2. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 2002;109:571-577
3. Tarran R, Grubb BR, Gatzy JT, Davis CW, Boucher RC. The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition. J Gen Physiol 2001; 118:223-236
4. Boucher RC, Stutts MJ, Knowles MR, Cantley L, Gatzy JT. Na1 transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. J Clin Invest 1986;78: 1245-1252
5. Stutts MJ, Canessa CM, Olsen JC, Hamrick M, Cohn JA, Rossier BC, Boucher RC. CFTR as a cAMP-dependent regulator of sodium channels. Science 1995;269:847-850
6. Boucher RC. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med 2007;58:157-170
7. Vallet V, Chraibi A, Gaeggeler HP, Horisberger JD, Rossier BC. An epithelial serine protease activates the amiloride-sensitive sodium channel. Nature 1997;389:607-610
8. Sheng S, Carattino MD, Bruns JB, Hughey RP, Kleyman TR. Furin cleavage activates the epithelial Na1 channel by relieving Na1 selfinhibition. Am J Physiol Renal Physiol 2006;290:F1488-F1496
9. Nimishakavi S, Besprozvannaya M, Raymond WW, Craik CS, Gruenert DC, Caughey GH. Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2012;303:L97-L106
10. Myerburg MM, McKenna EE, Luke CJ, Frizzell RA, Kleyman TR, Pilewski JM. Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2008;294:L932-L941
11. Ornatowski W, Poschet JF, Perkett E, Taylor-Cousar JL, Deretic V. Elevated furin levels in human cystic fibrosis cells result in hypersusceptibility to exotoxin A-induced cytotoxicity. J Clin Invest 2007;117:3489-3497
12. Bruns JB, Carattino MD, Sheng S, Maarouf AB, Weisz OA, Pilewski JM, Hughey RP, Kleyman TR. Epithelial Na1 channels are fully activated by furin-and prostasin-dependent release of an inhibitory peptide from the gamma-subunit. J Biol Chem 2007;282:6153-6160
13. Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol 2004;287:L928-L935
14. Coote K, Atherton-Watson HC, Sugar R, Young A, MacKenzie-Beevor A, Gosling M, Bhalay G, Bloomfield G, Dunstan A, Bridges RJ, et al. Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease. J Pharmacol Exp Ther 2009;329:764-774
15. Rowe SM, Reeves G, Hathorne H, Solomon GM, Abbi S, Renard D, Lock R, Zhou P, Danahay H, Clancy JP, et al. Reduced sodium transport with nasal administration of the prostasin inhibitor camostat in subjects with cystic fibrosis. Chest 2013;144:200-207
16. Myerburg MM, Harvey PR, Heidrich EM, Pilewski JM, Butterworth MB. Acute regulation of the epithelial sodium channel in airway epithelia by proteases and trafficking. Am J Respir Cell Mol Biol 2010;43: 712-719
17. Reihill JA, Walker B, Harvey B, Stutts J, Elborn JS, Martin SL. A novel inhibitor of channel activating proteases: putting the cap on ENaC. Pediatr Pulmonol 2015;50:229
18. Reihill JA, Walker B, Martin L, Elborn S. Channel activating proteases (CAPs): identification of novel targets for correcting sodium channel dysfunction in cystic fibrosis. Pediatr Pulmonol 2012;47: 262-263
19. Gilmore BF, Quinn DJ, Duff T, Cathcart GR, Scott CJ, Walker B. Expedited solid-phase synthesis of fluorescently labeled and biotinylated aminoalkane diphenyl phosphonate affinity probes for chymotrypsin-and elastase-like serine proteases. Bioconjug Chem 2009;20:2098-2105
20. Hamilton R, Walker BJ, Walker B. A convenient synthesis of N-protected diphenyl phosphonate ester analogs of ornithine, lysine and homolysine. Tetrahedron Lett 1993;34:2847-2850
21. Verriere V, Higgins G, Al-Alawi M, Costello RW, McNally P, Chiron R, Harvey BJ, Urbach V. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia. PLoS One 2012;7:e37746
22. Molloy SS, Bresnahan PA, Leppla SH, Klimpel KR, Thomas G. Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. J Biol Chem 1992;267:16396-16402
23. Iglewski BH, Kabat D. NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin. Proc Natl Acad Sci USA 1975;72: 2284-2288
24. Inocencio NM, Moehring JM, Moehring TJ. Furin activates Pseudomonas exotoxin A by specific cleavage in vivo and in vitro. J Biol Chem 1994;269:31831-31835
25. Jaffar-Bandjee MC, Lazdunski A, Bally M, Carrere J, Chazalette JP, Galabert C. Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa. J Clin Microbiol 1995;33:924-929
26. Klinger JD, Straus DC, Hilton CB, Bass JA. Antibodies to proteases and exotoxin A of Pseudomonas aeruginosa in patients with cystic fibrosis: demonstration by radioimmunoassay. J Infect Dis 1978;138: 49-58
27. Butterworth MB, Edinger RS, Johnson JP, Frizzell RA. Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool. J Gen Physiol 2005;125: 81-101
28. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Ďrevínek P, Griese M, McKone EF, Wainwright CE, Konstan MW, et al.; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365: 1663-1672
29. Grubb BR, Boucher RC. Pathophysiology of gene-targeted mouse models for cystic fibrosis. Physiol Rev 1999;79(Suppl. 1):S193-S214
30. Mall M, Grubb BR, Harkema JR, O'Neal WK, Boucher RC. Increased airway epithelial Na1 absorption produces cystic fibrosis-like lung disease in mice. Nat Med 2004;10:487-493
31. Zhou Z, Treis D, Schubert SC, Harm M, Schatterny J, Hirtz S, Duerr J, Boucher RC, Mall MA. Preventive but not late amiloride therapy reduces morbidity and mortality of lung disease in bENaC-overexpressing mice. Am J Respir Crit Care Med 2008;178:1245-1256
32. Mall MA, Button B, Johannesson B, Zhou Z, Livraghi A, Caldwell RA, Schubert SC, Schultz C, O'Neal WK, Pradervand S, et al. Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with bENaC-overexpressing mice. J Biol Chem 2010;285:26945-26955
33. Myerburg MM, Butterworth MB, McKenna EE, Peters KW, Frizzell RA, Kleyman TR, Pilewski JM. Airway surface liquid volume regulates ENaC by altering the serine protease-protease inhibitor balance: a mechanism for sodium hyperabsorption in cystic fibrosis. J Biol Chem 2006;281:27942-27949
34. Chen CJ, Wu BY, Tsao PI, Chen CY, Wu MH, Chan YL, Lee HS, Johnson MD, Eckert RL, Chen YW, et al. Increased matriptase zymogen activation in inflammatory skin disorders. Am J Physiol Cell Physiol 2011;300:C406-C415
35. Yasuoka S, Ohnishi T, Kawano S, Tsuchihashi S, Ogawara M, Masuda K, Yamaoka K, Takahashi M, Sano T. Purification, characterization, and localization of a novel trypsin-like protease found in the human airway. Am J Respir Cell Mol Biol 1997;16:300-308
36. Arkwright PD, Laurie S, Super M, Pravica V, Schwarz MJ, Webb AK, Hutchinson IV. TGF-b1 genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax 2000;55: 459-462
37. Blanchette F, Day R, Dong W, Laprise MH, Dubois CM. TGFb1 regulates gene expression of its own converting enzyme furin. J Clin Invest 1997;99:1974-1983
38. Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 2002;3: 753-766
39. Davies JC. Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respir Rev 2002;3:128-134
40. Miyazaki S, Matsumoto T, Tateda K, Ohno A, Yamaguchi K. Role of exotoxin A in inducing severe Pseudomonas aeruginosa infections in mice. J Med Microbiol 1995;43:169-175
41. Woods DE, Cryz SJ, Friedman RL, Iglewski BH. Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats. Infect Immun 1982;36:1223-1228
42. Carattino MD, Hughey RP, Kleyman TR. Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation. J Biol Chem 2008;283:25290-25295
43. Garland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, et al. Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways. Proc Natl Acad Sci USA 2013;110:15973-15978
44. Gentzsch M, Dang H, Dang Y, Garcia-Caballero A, Suchindran H, Boucher RC, Stutts MJ. The cystic fibrosis transmembrane conductance regulator impedes proteolytic stimulation of the epithelial Na1 channel. J Biol Chem 2010;285:32227-32232
45. Hughey RP, Bruns JB, Kinlough CL, Kleyman TR. Distinct pools of epithelial sodium channels are expressed at the plasma membrane. J Biol Chem 2004;279:48491-48494
46. Harris M, Garcia-Caballero A, Stutts MJ, Firsov D, Rossier BC. Preferential assembly of epithelial sodium channel (ENaC) subunits in Xenopus oocytes: role of furin-mediated endogenous proteolysis. J Biol Chem 2008;283:7455-7463
47. Tan CD, Hobbs C, Sameni M, Sloane BF, Stutts MJ, Tarran R. Cathepsin B contributes to Na1 hyperabsorption in cystic fibrosis airway epithelial cultures. J Physiol 2014;592:5251-5268
48. Caldwell RA, Boucher RC, Stutts MJ. Neutrophil elastase activates near-silent epithelial Na1 channels and increases airway epithelial Na1 transport. Am J Physiol Lung Cell Mol Physiol 2005;288: L813-L819
49. Harris M, Firsov D, Vuagniaux G, Stutts MJ, Rossier BC. A novel neutrophil elastase inhibitor prevents elastase activation and surface cleavage of the epithelial sodium channel expressed in Xenopus laevis oocytes. J Biol Chem 2007;282:58-64
50. Hughey RP, Bruns JB, Kinlough CL, Harkleroad KL, Tong Q, Carattino MD, Johnson JP, Stockand JD, Kleyman TR. Epithelial sodium channels are activated by furin-dependent proteolysis. J Biol Chem 2004;279:18111-18114
51. Mall MA, Hartl D. CFTR: cystic fibrosis and beyond. Eur Respir J 2014; 44:1042-1054
52. Ghosh A, Boucher RC, Tarran R. Airway hydration and COPD. Cell Mol Life Sci 2015;72:3637-3652
53. Liu C, Li Q, Zhou X, Kolosov VP, Perelman JM. Human airway trypsin-like protease induces mucin5AC hypersecretion via a protease-activated receptor 2-mediated pathway in human airway epithelial cells. Arch Biochem Biophys 2013;535: 234-240
54. Chokki M, Yamamura S, Eguchi H, Masegi T, Horiuchi H, Tanabe H, Kamimura T, Yasuoka S. Human airway trypsin-like protease increases mucin gene expression in airway epithelial cells. Am J Respir Cell Mol Biol 2004;30:470-478
55. Iwakiri K, Ghazizadeh M, Jin E, Fujiwara M, Takemura T, Takezaki S, Kawana S, Yasuoka S, Kawanami O. Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris. J Invest Dermatol 2004;122:937-944
56. Matsushima R, Takahashi A, Nakaya Y, Maezawa H, Miki M, Nakamura Y, Ohgushi F, Yasuoka S. Human airway trypsin-like protease stimulates human bronchial fibroblast proliferation in a proteaseactivated receptor-2-dependent pathway. Am J Physiol Lung Cell Mol Physiol 2006;290:L385-L395