Gel-forming mucins form distinct morphologic structures in airways

Proceedings of the National Academy of Sciences of the United States of America

Volumn 114, Issue 26, 2017, Pages 6842-6847

  Ostedgaard, Lynda S ^a   Moninger, Thomas O ^a   McMenimen, James D ^a   Sawin, Nicholas M ^a   Parker, Connor P ^a   Thornell, Ian M ^a   Powers, Linda S ^a   Gansemer, Nicholas D ^a   Bouzek, Drake C ^a   Cook, Daniel P ^a   Meyerholz, David K ^a   Alaiwa, Mahmoud H Abou ^a   Stoltz, David A ^a,b   Welsh, Michael J ^a,b  

^a UNIVERSITY OF IOWA   (United States)

^b University of Iowa   (United States)

Author keywords

Asthma; COPD; Cystic fibrosis; Lung; Mucus

Indexed keywords

LECTIN; MUCIN 5AC; MUCIN 5B; WHEAT GERM AGGLUTININ; MUC5AC PROTEIN, MOUSE; MUC5B PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CLINICAL FEATURE; COATED PARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CYSTIC FIBROSIS; GEL; GOBLET CELL; LUNG CLEARANCE; LUNG MUCOSA; MATERIAL COATING; MUCOUS CELL; MUCUS; NEWBORN; NONHUMAN; PIG; PRIORITY JOURNAL; PROTEIN INTERACTION; SUBMUCOSA; TRACHEA; AIRWAY REMODELING; ANIMAL; GENETICS; KNOCKOUT MOUSE; METABOLISM; MOUSE; PATHOLOGY;

AIRWAY REMODELING; ANIMALS; CYSTIC FIBROSIS; GOBLET CELLS; MICE; MICE, KNOCKOUT; MUCIN 5AC; MUCIN-5B;

EID: 85021433033     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1703228114     Document Type: Article

References (43)

1. Widdicombe JH, Wine JJ (2015) Airway gland structure and function. Physiol Rev 95: 1241-1319.
2. Wanner A, Salathé M, O'Riordan TG (1996) Mucociliary clearance in the airways. Am J Respir Crit Care Med 154:1868-1902.
3. Robinson M, Bye PT (2002) Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol 33:293-306.
4. Thornton DJ, Rousseau K, McGuckin MA (2008) Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol 70:459-486.
5. Fahy JV, Dickey BF (2010) Airway mucus function and dysfunction. N Engl J Med 363: 2233-2247.
6. Ambort D, Johansson ME, Gustafsson JK, Ermund A, Hansson GC (2012) Perspectives on mucus properties and formation-Lessons from the biochemical world. Cold Spring Harb Perspect Med 2:a014159.
7. Verdugo P (2012) Supramolecular dynamics of mucus. Cold Spring Harb Perspect Med 2:a009597.
8. Lillehoj EP, Kato K, Lu W, Kim KC (2013) Cellular and molecular biology of airway mucins. Int Rev Cell Mol Biol 303:139-202.
9. Turner J, Jones CE (2009) Regulation of mucin expression in respiratory diseases. Biochem Soc Trans 37:877-881.
10. Roy MG, et al. (2014) Muc5b is required for airway defence. Nature 505:412-416.
11. Evans CM, Kim K, Tuvim MJ, Dickey BF (2009) Mucus hypersecretion in asthma: Causes and effects. Curr Opin Pulm Med 15:4-11.
12. Lachowicz-Scroggins ME, et al. (2016) Abnormalities in MUC5AC and MUC5B protein in airway mucus in asthma. Am J Respir Crit Care Med 194:1296-1299.
13. Voynow JA, Gendler SJ, Rose MC (2006) Regulation of mucin genes in chronic inflammatory airway diseases. Am J Respir Cell Mol Biol 34:661-665.
14. Evans CM, et al. (2016) Idiopathic pulmonary fibrosis: A genetic disease that involves mucociliary dysfunction of the peripheral airways. Physiol Rev 96:1567-1591.
15. McShane D, et al. (2004) Normal nasal mucociliary clearance in CF children: Evidence against a CFTR-related defect. Eur Respir J 24:95-100.
16. Regnis JA, et al. (1994) Mucociliary clearance in patients with cystic fibrosis and in normal subjects. Am J Respir Crit Care Med 150:66-71.
17. Stoltz DA, Meyerholz DK, Welsh MJ (2015) Origins of cystic fibrosis lung disease. N Engl J Med 372:351-362.
18. Rogers CS, et al. (2008) Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321:1837-1841.
19. Stoltz DA, et al. (2010) Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2:29ra31.
20. Ostedgaard LS, et al. (2011) The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs. Sci Transl Med 3:74ra24.
21. Hoegger MJ, et al. (2014) Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science 345:818-822.
22. Hoegger MJ, et al. (2014) Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs. Proc Natl Acad Sci USA 111:2355-2360.
23. Trout L, Gatzy JT, Ballard ST (1998) Acetylcholine-induced liquid secretion by bronchial epithelium: Role of Cl-and HCO3-transport. Am J Physiol 275:L1095-L1099.
24. Ballard ST, Spadafora D (2007) Fluid secretion by submucosal glands of the tracheobronchial airways. Respir Physiol Neurobiol 159:271-277.
25. Grubb BR, Boucher RC (1999) Pathophysiology of gene-targeted mouse models for cystic fibrosis. Physiol Rev 79(1, Suppl):S193-S214.
26. Voynow JA, Rubin BK (2009) Mucins, mucus, and sputum. Chest 135:505-512.
27. Rogers CS, et al. (2008) The porcine lung as a potential model for cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 295:L240-L263.
28. Meyerholz DK, et al. (2010) 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 182:1251-1261.
29. Tang XX, et al. (2016) Acidic pH increases airway surface liquid viscosity in cystic fibrosis. J Clin Invest 126:879-891.
30. Joo NS, Cho HJ, Khansaheb M, Wine JJ (2010) Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs. J Clin Invest 120:3161-3166.
31. Lee RJ, Foskett JK (2010) cAMP-activated Ca2+ signaling is required for CFTRmediated serous cell fluid secretion in porcine and human airways. J Clin Invest 120:3137-3148.
32. Meyerholz DK, Stoltz DA, Pezzulo AA, Welsh MJ (2010) Pathology of gastrointestinal organs in a porcine model of cystic fibrosis. Am J Pathol 176:1377-1389.
33. Smith JJ, Welsh MJ (1992) cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. J Clin Invest 89:1148-1153.
34. Poulsen JH, Fischer H, Illek B, Machen TE (1994) Bicarbonate conductance and pH regulatory capability of cystic fibrosis transmembrane conductance regulator. Proc Natl Acad Sci USA 91:5340-5344.
35. Song Y, Salinas D, Nielson DW, Verkman AS (2006) Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis. Am J Physiol Cell Physiol 290:C741-C749.
36. Gustafsson JK, et al. (2012) Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J Exp Med 209:1263-1272.
37. Garcia MA, Yang N, Quinton PM (2009) Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest 119:2613-2622.
38. Yang N, Garcia MA, Quinton PM (2013) Normal mucus formation requires cAMPdependent HCO3-secretion and Ca2+-mediated mucin exocytosis. J Physiol 591: 4581-4593.
39. Flores-Delgado G, Lytle C, Quinton PM (2016) Site of fluid secretion in small airways. Am J Respir Cell Mol Biol 54:312-318.
40. Mandal C, Mandal C (1990) Sialic acid binding lectins. Experientia 46:433-441.
41. Tachibana K, et al. (2006) Elucidation of binding specificity of Jacalin toward O-glycosylated peptides: Quantitative analysis by frontal affinity chromatography. Glycobiology 16:46-53.
42. Roth J (2011) Lectins for histochemical demonstration of glycans. Histochem Cell Biol 136:117-130.
43. Howat WJ, Wilson BA (2014) Tissue fixation and the effect of molecular fixatives on downstream staining procedures. Methods 70:12-19.