Role of epidermal growth factor receptor activation in regulating mucin synthesis

Respiratory Research

Jay A Nadel¹ 

[1] Cardiovascular Research Institute, Departments of Medicine and Physiology, University of California, San Francisco, California, USA

关键词: tumor necrosis factor-α;    oxygen free radical;    nasal polyp;    cigarette smoke;    chronic intubation;    asthma;    airway goblet cell;    activated neutrophils;   

Others  :  1227461
DOI  :  10.1186/rr43

 received in 2001-01-10, accepted in 2001-02-02,  发布年份 2001

【 摘 要 】

Healthy individuals have few goblet cells in their airways, but in patients with hypersecretory diseases goblet-cell upregulation results in mucus hypersecretion, airway plugging, and death. Multiple stimuli produce hypersecretion via epidermal growth factor receptor (EGFR) expression and activation, causing goblet-cell metaplasia from Clara cells by a process of cell differentiation. These cells are also believed to be the cells of origin of non-small-cell lung cancer, but this occurs via cell multiplication. The mechanisms that determine which pathway is chosen are critical but largely unknown. Although no effective therapy exists for hypersecretion at present, the EGFR cascade suggests methods for effective therapeutic intervention.

【 授权许可】

   
2001 BioMed Central Ltd

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Cohen S: Epidermal growth factor. Nobel Lecture. Biosci Rep 1986, 6:1017-1028.
• [2]McDowell EM, Trump BF: Histogenesis of preneoplastic lesions in tracheobronchial epithelium. Surv Synth Pathol Res 1983, 2:235-279.
• [3]Greenberg SD, Smith MN, Spjut HJ: Bronchiolo-alveolar carcinoma-cell of origin. Am J Clin Pathol 1975, 63:153-167.
• [4]Takeyama K, Dabbagh K, Lee H-M, Agusti C, Lausier JA, Ueki IF, Grattan KM, Nadel JA: Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci USA 1999, 96:3081-3086.
• [5]Royce FH, Basbaum CB: Analysis of thymidine incorporation by airway epithelial cells in a rat model of chronic bronchitis [abstract]. Am Rev Respir Dis 1990, 141:A107.
• [6]Shimizu T, Takahashi Y, Kawaguchi S, Sakakura Y: Hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium induced by endotoxin. Am J Respir Crit Care Med 1996, 153:1412-1418.
• [7]Cardell BS, Pearson RSB: Death in asthmatics. Thorax 1959, 14:341-352.
• [8]Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T: Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe asthma attack. Chest 1992, 1101:916-921.
• [9]Burgel P-R, Escudier E, Coste A, Dao-Pick T, Ueki IF, Takeyama K, Shim JJ, Murr AH, Nadel JA: Relation of EGF receptor expression to goblet cell hyperplasia in nasal polyps. J Allergy Clin Immunol 2000, 106:705-712.
• [10]Boucher RC, Knowles MR, Yankaskas JR: Cystic fibrosis.7. In: Textbook of Respiratory Medicine, 3rd ed. Edited by Murray JF, Nadel JA. Philadelphia, PA: WB Saunders Co; 2000, 1291-1323.
• [11]Piquette CA, Rennard SI, Snider GL: Chronic bronchitis and emphysema. In: Textbook of Respiratory Medicine, 3rd ed. Edited by Murray JF, Nadel JA. Philadelphia, PA: WB Saunders Co; 2000, 1187-1245.
• [12]Cosio MG, Hale KA, Niewoehner DE: Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. Am Rev Respir Dis 1980, 122:265-271.
• [13]Coles SJ, Levine LR, Reid L: Hypersecretion of mucus glycoproteins in rat airways induced by tobacco smoke. Am J Pathol 1979, 94:459-471.
• [14]Heath RB, Steffey EP, Thurmon JC, Wertz EM, Meagher DM, Hyppa T, Van Slyke GL: Laryngotracheal lesions following routine orotracheal intubation in the horse. Equine Vet J 1989, 21:434-437.
• [15]Keenan KP, Wilson TS, McDowell EM: Regeneration of hamster tracheal epithelium after mechanical injury. IV. Histochemical, immunocytochemical and ultrastructural studies. Virchows Arch [Cell Pathol] 1983, 43:213-240.
• [16]Lee H-M, Takeyama K, Dabbagh K, Lausier JA, Ueki IF, Nadel JA: Agarose plug instillation causes goblet cell metaplasia by activating EGF receptors in rat airways. Am J Physiol Lung Cell Mol Physiol 2000, 278:L185-L192.
• [17]Fahy JV, Kim KW, Liu J, Boushey HA: Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol 1995, 95:843-852.
• [18]Amishima M, Munakata M, Nasuhara Y, Sato A, Takahashi T, Homma Y, Kawakami Y: Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway. Am J Respir Crit Care Med 1998, 57:1907-1912.
• [19]Takeyama K, Fahy JV, Nadel JA: Relationship of epidermal growth factor receptors to airway goblet cell production. Am J Respir Crit Care Med 2001, 163:1-6.
• [20]Elovic A, Wong DTW, Weller PF, Matossian K, Galli SJ: Expression of transforming growth factors-alpha and beta-1 messenger RNA and product by eosinophils in nasal polyps. J Allergy Clin Immunol 1994, 93:864-869.
• [21]Takeyama K, Dabbagh K, Shim JJ, Dao-Pick T, Ueki IF, Nadel JA: Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor: role of neutrophils. J Immunol 2000, 164:1546-1552.
• [22]Blyth DI, Pedrick MS, Savage TJ, Hessel EM, Fattah D: Lung inflammation and epithelial changes in a murine model of atopic asthma. Am J Respir Cell Mol Biol 1996, 14:425-438.
• [23]Grunig G, Warnock M, Wakil A, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB: Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1999, 282:2261-2263.
• [24]Cohn L, Homer RJ, MacLeod H, Mohrs M, Brombacher F, Bottomly K: Th2-induced airway mucus production is dependent on IL-4Rα, but not on eosinophils. J Immunol 1999, 162:6178-6183.
• [25]Gavett SH, O'Hearn DJ, Karp CL, Patel EA, Schofield BH, Finkelman FD, Wills-Karp M: Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice. Am J Physiol Lung Cell Mol Physiol 1997, 272:L253-L261.
• [26]Shim JJ, Dabbagh K, Ueki IF, Dao-Pick T, Burgel P-R, Takeyama K, Tam DC-W, Nadel JA: Interleukin-13 induces mucus production by stimulating epidermal growth factor receptors and by activating neutrophils. Am J Physiol Lung Cell Mol Physiol 2001, 280:L134-L140.
• [27]Takeyama K, Jung B, Shim JJ, Burgel P-R, Dao-Pick T, Ueki IF, Protin U, Kroschel P, Nadel JA: Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol 2001, 280:L165-L172.
• [28]Borchers MT, Wert SE, Leikauf GD: Acrolein-induced MUC5AC expression in rat airways. Am J Physiol Lung Cell Mol Physiol 1998, 274:L573-L581.
• [29]Barrow RE, Wang C, Evans MJ, Herndon DN: Growth factors accelerate epithelial repair in sheep trachea. Lung 1993, 171:335-344.
• [30]Puddicombe SM, Polosa R, Richter A, Krishna MT, Howarth PH, Holgate ST, Davis DE: Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J 2000, 14:1362-1374.
• [31]Harkema JR, Hotchkiss JA: In vivo effects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways. Quantitative histochemistry. Am J Pathol 1992, 141:307-317.
• [32]Shimizu T, Takahashi Y, Kawaguchi S, Sakakura Y: Hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium induced by endotoxin. Am J Respir Crit Care Med 1996, 153:1412-1418.
• [33]Steiger D, Hotchkiss J, Bajaj L, Harkema J, Basbaum C: Concurrent increases in the storage and release of mucin-like molecules by rat airway epithelial cells in response to bacterial endotoxin. Am J Respir Cell Mol Biol 1995, 12:307-314.
• [34]Li J-D, Dohrman AF, Gallup M, Miyata S, Gum JR, Kim YS, Nadel JA, Prince A, Basbaum CB: Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci USA 1997, 94:967-972.
• [35]Li J-D, Fang W, Gallup M, Kim J-H, Gum J, Kim Y, Basbaum C: Activation of NF-κB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa -induced mucin overproduction in epithelial cells. Proc Natl Acad Sci USA 1998, 95:5718-5723.
• [36]Kohri K, Ueki IF, Shim JJ, Burgel P-R, Oh YM, Tam DC, Dao-Pick T, Nadel JA: Pseudomonas aeruginosa (PA) exoproducts induce mucin MUC5AC production via expression and activation of epidermal growth factor receptor (EGFR). Am J Respir Crit Care Med 2001, in press.
• [37]Verdugo P: Goblet cells secretion and mucogenesis. Annu Rev Physiol 1990, 52:157-176.
• [38]Shimura S, Andoh Y, Haraguchi M, Shirato K: Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma. Eur Respir J 1996, 9:1395-1401.