CFTR: Cystic fibrosis and beyond

European Respiratory Journal

Volumn 44, Issue 4, 2014, Pages 1042-1054

  Mall, Marcus A ^a   Hartl, Dominik ^b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMILORIDE; CHLORIDE CHANNEL; CHLORIDE CHANNEL AFFECTING AGENT; CRISPR ASSOCIATED PROTEIN; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; EPITHELIAL SODIUM CHANNEL BLOCKING AGENT; IVACAFTOR; LENTIVIRUS VECTOR; LUMICAFTOR; SLC26A9; TMEM16A; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR NUCLEASE; UNCLASSIFIED DRUG; ZINC FINGER NUCLEASE;

ARTICLE; BACTERIAL INFECTION; CHRONIC OBSTRUCTIVE LUNG DISEASE; CYSTIC FIBROSIS; DRUG TARGETING; FATALITY; GENE MUTATION; GENETIC DISORDER; HUMAN; IN VIVO STUDY; INFLAMMATION; LUNG DISEASE; MUCUS SECRETION; NONHUMAN; NONVIRAL GENE THERAPY; OBSTRUCTION; PATHOGENESIS; PLURIPOTENT STEM CELL; RESPIRATORY TRACT DISEASE; RESPIRATORY TRACT INFECTION; STEM CELL TRANSPLANTATION; VIRAL GENE THERAPY; GENETICS; MUTATION; PATHOPHYSIOLOGY;

CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMANS; MUTATION;

EID: 84905655597     PISSN: 09031936     EISSN: 13993003     Source Type: Journal    
DOI: 10.1183/09031936.00228013     Document Type: Article

References (135)

1. Rommens JM, Iannuzzi MV, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989; 245: 1059-1065.
2. Riordan JR, Rommens JM, Kerem BS, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989; 245: 1066-1072.
3. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 245: 1073-1080.
4. Riordan JR. CFTR function and prospects for therapy. Annu Rev Biochem 2008; 77: 701-726.
5. Kreda SM, Mall M, Mengos A, et al. Characterization of wild-type and DF508 cystic fibrosis transmembrane regulator in human respiratory epithelia. Mol Biol Cell 2005; 16: 2154-2167.
6. Anderson MP, Gregory RJ, Thompson S, et al. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 1991; 253: 202-205.
7. Smith JJ, Welsh MJ. cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. J Clin Invest 1992; 89: 1148-1153.
8. Stutts MJ, Canessa CM, Olsen JC, et al. CFTR as a cAMP-dependent regulator of sodium channels. Science 1995; 269: 847-850.
9. Hopf A, Schreiber R, Mall M, et al. Cystic fibrosis transmembrane conductance regulator inhibits epithelial Na+ channels carrying Liddle's syndrome mutations. J Biol Chem 1999; 274: 13894-13899.
10. Knowles MR, Gatzy JT, Boucher RC. Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis. N Engl J Med 1981; 305: 1489-1495.
11. Boucher RC, Stutts MJ, Knowles MR, et al. Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. J Clin Invest 1986; 78: 1245-1252.
12. Mall M, Bleich M, Greger R, et al. The amiloride inhibitable Na+ conductance is reduced by CFTR in normal but not in cystic fibrosis airways. J Clin Invest 1998; 102: 15-21.
13. Sheppard DN, Rich DP, Ostedgaard LS, et al. Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties. Nature 1993; 362: 160-164.
14. Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 1993; 73: 1251-1254.
15. Sosnay PR, Siklosi KR, Van Goor F, et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 2013; 45: 1160-1167.
16. Matsui H, Grubb BR, Tarran R, et al. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 1998; 95: 1005-1015.
17. Mall M, Grubb BR, Harkema JR, et al. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 2004; 10: 487-493.
18. Stoltz DA, Meyerholz DK, Pezzulo AA, et al. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2010; 2: 29-31.
19. Boucher RC. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med 2007; 58: 157-170.
20. Mall MA. Role of cilia, mucus, and airway surface liquid in mucociliary dysfunction: lessons from mouse models. J Aerosol Med Pulm Drug Deliv 2008; 21: 13-24.
21. Clarke LL, Grubb BR, Yankaskas JR, et al. Relationship of a non-cystic fibrosis transmembrane conductance regulator-mediated chloride conductance to organ-level disease in Cftr (-/-) mice. Proc Natl Acad Sci USA 1994; 91: 479-483.
22. Zhou Z, Duerr J, Johannesson B, et al. The bENaC-overexpressing mouse as a model of cystic fibrosis lung disease. J Cyst Fibros 2011; 10: Suppl. 2, S172-S182.
23. Rogers CS, Stoltz DA, Meyerholz DK, et al. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 2008; 321: 1837-1841.
24. Sun X, Sui H, Fisher JT, et al. Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. J Clin Invest 2010; 120: 3149-3160.
25. Klymiuk N, Mundhenk L, Kraehe K, et al. Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis. J Mol Med (Berl) 2012; 90: 597-608.
26. Livraghi-Butrico A, Kelly EJ, Klem ER, et al. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation. Mucosal Immunol 2012; 5: 397-408.
27. Mall MA, Graeber SY, Stahl M, et al. Early cystic fibrosis lung disease: role of airway surface dehydration and lessons from preventive rehydration therapies in mice. Int J Biochem Cell Biol 2014; 52: 174-179.
28. Grasemann H, Ratjen F. Early lung disease in cystic fibrosis. Lancet Respir Med 2013; 1: 148-157.
29. Zuelzer WW, Newton WA. The pathogenesis of fibrocystic disease of the pancreas: a study of 36 cases with special reference to the pulmonary lesions. Pediatrics 1949; 4: 53-69.
30. Mall MA, Harkema JR, Trojanek JB, et al. Development of chronic bronchitis and emphysema in b-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med 2008; 177: 730-742.
31. Wielpütz MO, Eichinger M, Zhou Z, et al. In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography. Eur Respir J 2011; 38: 1060-1070.
32. Gehrig S, Duerr J, Weitnauer M, et al. Lack of neutrophil elastase reduces inflammation, mucus hypersecretion and emphysema, but not mucus obstruction, in mice with CF-like lung disease. Am J Respir Crit Care Med 2014; 189: 1082-1092.
33. Trojanek JB, Cobos-Correa A, Diemer S, et al. Airway mucus obstruction triggers macrophage activation and MMP12-dependent emphysema. Am J Respir Cell Mol Biol 2014 [In press DOI: 10.1165/rcmb.2013-0407OC].
34. Pezzulo AA, Tang XX, Hoegger MJ, et al. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 2012; 487: 109-113.
35. Sun X, Olivier AK, Liang B, et al. Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets. Am J Respir Cell Mol Biol 2014; 50: 502-512.
36. Chen JH, Stoltz DA, Karp PH, et al. Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia. Cell 2010; 143: 911-923.
37. Joo NS, Cho HJ, Khansaheb M, et al. Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs. J Clin Invest 2010; 120: 3161-3166.
38. Sly PD, Gangell CL, Chen L, et al. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013; 368: 1963-1970.
39. Voynow JA, Fischer BM, Zheng S. Proteases and cystic fibrosis. Int J Biochem Cell Biol 2008; 40: 1238-1245.
40. Belaaouaj A, McCarthy R, Baumann M, et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med 1998; 4: 615-618.
41. Shapiro SD, Goldstein NM, Houghton AM, et al. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol 2003; 163: 2329-2335.
42. Hartl D, Latzin P, Hordijk P, et al. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. Nat Med 2007; 13: 1423-1430.
43. Caldwell RA, Boucher RC, Stutts MJ. Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport. Am J Physiol Lung Cell Mol Physiol 2005; 288: L813-L819.
44. Gaillard EA, Kota P, Gentzsch M, et al. Regulation of the epithelial Na+ channel and airway surface liquid volume by serine proteases. Pflugers Arch 2010; 460: 1-17.
45. Gentzsch M, Dang H, Dang Y, et al. The cystic fibrosis transmembrane conductance regulator impedes proteolytic stimulation of the epithelial Na+ channel. J Biol Chem 2010; 285: 32227-32232.
46. Haerteis S, Krappitz M, Bertog M, et al. Proteolytic activation of the epithelial sodium channel (ENaC) by the cysteine protease cathepsin-S. Pflugers Arch 2012; 464: 353-365.
47. Le Gars M, Descamps D, Roussel D, et al. Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo. Am J Respir Crit Care Med 2013; 187: 170-179.
48. Button B, Cai LH, Ehre C, et al. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science 2012; 337: 937-941.
49. Dickey BF. Biochemistry. Walking on solid ground. Science 2012; 337: 924-925.
50. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med 2010; 363: 2233-2247.
51. Lohi H, Kujala M, Makela S, et al. Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9. J Biol Chem 2002; 277: 14246-14254.
52. Anagnostopoulou P, Dai L, Schatterny J, et al. Allergic airway inflammation induces a pro-secretory epithelial ion transport phenotype in mice. Eur Respir J 2010; 36: 1436-1447.
53. Anagnostopoulou P, Riederer B, Duerr J, et al. SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation. J Clin Invest 2012; 122: 3629-3634.
54. Coakley RD, Grubb BR, Paradiso AM, et al. Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium. Proc Natl Acad Sci USA 2003; 100: 16083-16088.
55. Garcia MA, Yang N, Quinton PM. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest 2009; 119: 2613-2622.
56. Gustafsson JK, Ermund A, Ambort D, et al. Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J Exp Med 2012; 209: 1263-1272.
57. Quinton PM. Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet 2008; 372: 415-417.
58. Lee TW, Southern KW. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease. Cochrane Database Syst Rev 2012; 10: CD005599.
59. Galietta LV, Jayaraman S, Verkman AS. Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists. Am J Physiol Cell Physiol 2001; 281: C1734-C1742.
60. Van Goor F, Straley KS, Cao D, et al. Rescue of DF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am J Physiol Lung Cell Mol Physiol 2006; 290: L1117-L1130.
61. Van Goor F, Hadida S, Grootenhuis PD, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 2009; 106: 18825-18830.
62. Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci USA 2011; 108: 18843-18848.
63. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663-1672.
64. Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013; 187: 1219-1225.
65. Jih KY, Hwang TC. VX-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle. Proc Natl Acad Sci USA 2013; 110: 4404-4409.
66. Davies J, Sheridan H, Bell N, et al. Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Lancet Respir Med 2013; 1: 630-638.
67. Donaldson SH, Bennett WD, Zeman KL, et al. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 2006; 354: 241-250.
68. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006; 354: 229-240.
69. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med 1994; 331: 637-642.
70. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999; 340: 23-30.
71. Becq F, Mall MA, Sheppard DN, et al. Pharmacological therapy for cystic fibrosis: from bench to bedside. J Cyst Fibros 2011; 10: Suppl. 2, S129-S145.
72. Sermet-Gaudelus I. Ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation. Eur Respir Rev 2013; 22: 66-71.
73. Clancy JP, Jain M. Personalized medicine in cystic fibrosis: dawning of a new era. Am J Respir Crit Care Med 2012; 186: 593-597.
74. Yu H, Burton B, Huang CJ, et al. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros 2012; 11: 237-245.
75. Van Goor F, Yu H, Burton B, et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros 2014; 13: 29-36.
76. Quinton P, Molyneux L, Ip W, et al. b-adrenergic sweat secretion as a diagnostic test for cystic fibrosis. Am J Respir Crit Care Med 2012; 186: 732-739.
77. Hirtz S, Gonska T, Seydewitz HH, et al. CFTR Cl- channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis. Gastroenterology 2004; 127: 1085-1095.
78. Roth EK, Hirtz S, Duerr J, et al. The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients. PLoS One 2011; 6: e24445.
79. Dekkers JF, Wiegerinck CL, De Jonge HR, et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med 2013; 19: 939-945.
80. Esterly JR, Oppenheimer EH. Cystic fibrosis of the pancreas: structural changes in peripheral airways. Thorax 1968; 23: 670-675.
81. Wielputz MO, Weinheimer O, Eichinger M, et al. Pulmonary emphysema in cystic fibrosis detected by densitometry on chest multidetector computed tomography. PLoS One 2013; 8: e73142.
82. Sly PD, Brennan S, Gangell C, et al. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009; 180: 146-152.
83. Eichinger M, Optazaite DE, Kopp-Schneider A, et al. Morphologic and functional scoring of cystic fibrosis lung disease using MRI. Eur J Radiol 2012; 81: 1321-1329.
84. Subbarao P, Stanojevic S, Brown M, et al. Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline. Am J Respir Crit Care Med 2013; 188: 456-460.
85. Stahl M, Joachim C, Blessing K, et al. Multiple breath washout is feasible in the clinical setting and detects abnormal lung function in infants and young children with cystic fibrosis. Respiration 2014; 87: 357-363.
86. Wielputz MO, Puderbach M, Kopp-Schneider A, et al. Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 2014; 189: 956-965.
87. Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 2012; 67: 12-18.
88. Mendoza JL, Schmidt A, Li Q, et al. Requirements for efficient correction of DF508 CFTR revealed by analyses of evolved sequences. Cell 2012; 148: 164-174.
89. Rabeh WM, Bossard F, Xu H, et al. Correction of both NBD1 energetics and domain interface is required to restore DF508 CFTR folding and function. Cell 2012; 148: 150-163.
90. Okiyoneda T, Veit G, Dekkers JF, et al. Mechanism-based corrector combination restores DF508-CFTR folding and function. Nat Chem Biol 2013; 9: 444-454.
91. Griesenbach U, Alton EW. Moving forward: cystic fibrosis gene therapy. Hum Mol Genet 2013; 22: R52-R58.
92. Lee CM, Flynn R, Hollywood JA, et al. Correction of the DF508 mutation in the cystic fibrosis transmembrane conductance regulator gene by zinc-finger nuclease homology-directed repair. Biores Open Access 2012; 1: 99-108.
93. Schwank G, Koo BK, Sasselli V, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 2013; 13: 653-658.
94. Kormann MS, Hasenpusch G, Aneja MK, et al. Expression of therapeutic proteins after delivery of chemically modified mRNA in mice. Nat Biotechnol 2011; 29: 154-157.
95. Schmeckebier S, Mauritz C, Katsirntaki K, et al. Keratinocyte growth factor and dexamethasone plus elevated cAMP levels synergistically support pluripotent stem cell differentiation into alveolar epithelial type II cells. Tissue Eng Part A 2013; 19: 938-951.
96. Wong AP, Bear CE, Chin S, et al. Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nat Biotechnol 2012; 30: 876-882.
97. Mall MA. Role of the amiloride-sensitive epithelial Na+ channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease. Exp Physiol 2009; 94: 171-174.
98. Pons G, Marchand MC, d'Athis P, et al. French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Pediatr Pulmonol 2000; 30: 25-31.
99. Zhou Z, Treis D, Schubert SC, et al. 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.
100. Hirsh AJ, Zang J, Zamurs A, et al. Pharmacological properties of 552-02, a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease. J Pharmacol Exp Ther 2008; 325: 77-88.
101. Hunt T, Atherton-Watson HC, Axford J, et al. Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: quaternary amines. Bioorg Med Chem Lett 2012; 22: 929-932.
102. Garcia-Caballero A, Rasmussen JE, Gaillard E, et al. SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage. Proc Natl Acad Sci USA 2009; 106: 11412-11417.
103. Gianotti A, Melani R, Caci E, et al. Epithelial sodium channel silencing as a strategy to correct the airway surface fluid deficit in cystic fibrosis. Am J Respir Cell Mol Biol 2013; 49: 445-452.
104. Almaca J, Faria D, Sousa M, et al. High-content siRNA screen reveals global ENaC regulators and potential cystic fibrosis therapy targets. Cell 2013; 154: 1390-1400.
105. O'Riordan TG, Donn KH, Hodsman P, et al. Acute hyperkalemia associated with inhalation of a potent ENaC antagonist: phase 1 trial of GS-9411. J Aerosol Med Pulm Drug Deliv 2014; 27: 200-208.
106. Anderson MP, Welsh MJ. Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia. Proc Natl Acad Sci 1991; 88: 6003-6007.
107. Knowles MR, Clarke LL, Boucher RC. Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med 1991; 325: 533-538.
108. Tarran R, Button B, Picher M, et al. Normal and cystic fibrosis airway surface liquid homeostasis. The effects of phasic shear stress and viral infections. J Biol Chem 2005; 280: 35751-35759.
109. Ratjen F, Durham T, Navratil T, et al. Long term effects of denufosol tetrasodium in patients with cystic fibrosis. J Cyst Fibros 2012; 11: 539-549.
110. Mundhenk L, Johannesson B, Anagnostopoulou P, et al. mCLCA3 does not contribute to calcium-activated chloride conductance in murine airways. Am J Respir Cell Mol Biol 2012; 47: 87-93.
111. Caputo A, Caci E, Ferrera L, et al. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 2008; 322: 590-594.
112. Rock JR, O'Neal WK, Gabriel SE, et al. Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways. J Biol Chem 2009; 284: 14875-14880.
113. Bakouh N, Bienvenu T, Thomas A, et al. Characterization of SLC26A9 in patients with CF-like lung disease. Hum Mutat 2013; 34: 1404-1414.
114. Sun L, Rommens JM, Corvol H, et al. Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat Genet 2012; 44: 562-569.
115. Hartl D, Gaggar A, Bruscia E, et al. Innate immunity in cystic fibrosis lung disease. J Cyst Fibros 2012; 11: 363-382.
116. Huaux F, Noel S, Dhooghe B, et al. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis. PLoS One 2013; 8: e64341.
117. Di A, Brown ME, Deriy LV, et al. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol 2006; 8: 933-944.
118. Zhou Y, Song K, Painter RG, et al. Cystic fibrosis transmembrane conductance regulator recruitment to phagosomes in neutrophils. J Innate Immun 2013; 5: 219-230.
119. Painter RG, Valentine VG, Lanson NA Jr, et al. CFTR expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis. Biochemistry 2006; 45: 10260-10269.
120. Bonfield TL, Hodges CA, Cotton CU, et al. Absence of the cystic fibrosis transmembrane regulator (CFTR) from myeloid-derived cells slows resolution of inflammation and infection. J Leukoc Biol 2012; 92: 1111-1122.
121. Phennicie RT, Sullivan MJ, Singer JT, et al. Specific resistance to Pseudomonas aeruginosa infection in zebrafish is mediated by the cystic fibrosis transmembrane conductance regulator. Infect Immun 2010; 78: 4542-4550.
122. Bonvin E, Le Rouzic P, Bernaudin JF, et al. Congenital tracheal malformation in cystic fibrosis transmembrane conductance regulator-deficient mice. J Physiol 2008; 586: 3231-3243.
123. Meyerholz DK, Stoltz DA, Namati E, et al. Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children. Am J Respir Crit Care Med 2010; 182: 1251-1261.
124. Adam RJ, Michalski AS, Bauer C, et al. Air trapping and airflow obstruction in newborn cystic fibrosis piglets. Am J Respir Crit Care Med 2013; 188: 1434-1441.
125. Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013; 187: 347-365.
126. Smaldone GC, Foster WM, O'Riordan TG, et al. Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease. Chest 1993; 103: 1390-1396.
127. Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 2009; 4: 435-459.
128. Cantin AM, Hanrahan JW, Bilodeau G, et al. Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Am J Respir Crit Care Med 2006; 173: 1139-1144.
129. Clunes LA, Davies CM, Coakley RD, et al. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J 2012; 26: 533-545.
130. Sloane PA, Shastry S, Wilhelm A, et al. A pharmacologic approach to acquired cystic fibrosis transmembrane conductance regulator dysfunction in smoking related lung disease. PLoS One 2012; 7: e39809.
131. Dransfield MT, Wilhelm AM, Flanagan B, et al. Acquired CFTR dysfunction in the lower airways in COPD. Chest 2013; 144: 498-506.
132. Hill DB, Vasquez PA, Mellnik J, et al. A biophysical basis for mucus solids concentration as a candidate biomarker for airways disease. PLoS One 2014; 9: e87681.
133. Bodas M, Min T, Mazur S, et al. Critical modifier role of membrane-cystic fibrosis transmembrane conductance regulator-dependent ceramide signaling in lung injury and emphysema. J Immunol 2011; 186: 602-613.
134. Bodas M, Min T, Vij N. Critical role of CFTR-dependent lipid rafts in cigarette smoke-induced lung epithelial injury. Am J Physiol Lung Cell Mol Physiol 2011; 300: L811-L820.
135. Raju SV, Jackson PL, Courville CA, et al. Cigarette smoke induces systemic defects in cystic fibrosis transmembrane conductance regulator function. Am J Respir Crit Care Med 2013; 188: 1321-1330.