Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium

P-R Burgel, J A Nadel, P-R Burgel, J A Nadel

Abstract

The epithelial cells lining the airways serve protective functions. The "barrier function" of the epithelium protects the individual from damage by inhaled irritants. The epithelium produces mucins which become hydrated and form a viscoelastic gel which spreads over the epithelial surface. In healthy individuals inhaled foreign materials become entrapped in the mucus and are cleared by mucociliary transport and by coughing. In many chronic inflammatory airway diseases, however, excessive mucus is produced and is inadequately cleared, leading to mucous obstruction and infection. At present there is no specific treatment for hypersecretion. However, the discovery that an epidermal growth factor receptor (EGFR) cascade is involved in mucin production by a wide variety of stimuli suggests that blockade may provide specific treatment for hypersecretory diseases. EGFR pathways have also been implicated in the repair of damaged airway epithelium. The roles of EGFR in airway epithelial cell hypersecretion and epithelial damage and repair are reviewed and future potential treatments are suggested.

References

    1. J Immunol. 2000 Feb 1;164(3):1546-52
    1. Nature. 1999 Dec 23-30;402(6764):884-8
    1. J Allergy Clin Immunol. 2000 Oct;106(4):705-12
    1. Am J Respir Cell Mol Biol. 2001 Feb;24(2):123-31
    1. Am J Respir Crit Care Med. 2001 Feb;163(2):511-6
    1. Am J Respir Crit Care Med. 2001 Feb;163(2):517-23
    1. J Immunol. 2001 Nov 15;167(10):5948-54
    1. Am J Respir Cell Mol Biol. 2001 Dec;25(6):739-43
    1. Nat Med. 2002 Jan;8(1):41-6
    1. Am J Respir Cell Mol Biol. 2002 Jul;27(1):85-90
    1. J Biol Chem. 2002 Aug 30;277(35):32258-67
    1. Glycoconj J. 2001 Sep;18(9):661-84
    1. Eur Respir J. 2002 Nov;20(5):1263-70
    1. Novartis Found Symp. 2002;248:3-12; discussion 12-9, 277-82
    1. N Engl J Med. 2003 Jul 24;349(4):350-7
    1. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11618-23
    1. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5813-24
    1. Am J Respir Cell Mol Biol. 2004 Apr;30(4):470-8
    1. Eur Respir J. 2004 Jul;24(1):1-2
    1. Am Rev Respir Dis. 1985 Apr;131(4):599-606
    1. Biosci Rep. 1986 Dec;6(12):1017-28
    1. Cell. 1988 Apr 22;53(2):285-93
    1. J Exp Med. 1990 Sep 1;172(3):673-81
    1. Lung. 1993;171(6):335-44
    1. J Cell Sci. 1993 Nov;106 ( Pt 3):869-78
    1. Am J Respir Cell Mol Biol. 1994 Nov;11(5):540-51
    1. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):967-72
    1. Am J Pathol. 1997 Aug;151(2):443-59
    1. J Clin Invest. 1997 Sep 1;100(5):1271-81
    1. Am J Respir Cell Mol Biol. 1998 Jan;18(1):66-74
    1. Proc Natl Acad Sci U S A. 1998 May 12;95(10):5718-23
    1. Am J Respir Cell Mol Biol. 1998 Jul;19(1):30-7
    1. Am J Respir Cell Mol Biol. 1998 Nov;19(5):786-98
    1. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3081-6
    1. Am J Respir Cell Mol Biol. 1999 Apr;20(4):787-96
    1. Curr Opin Cell Biol. 1999 Apr;11(2):184-9
    1. Am J Respir Cell Mol Biol. 1999 May;20(5):914-23
    1. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6235-40
    1. Adv Cancer Res. 2000;77:25-79
    1. FASEB J. 2000 Jul;14(10):1362-74

Source: PubMed

3
S'abonner