Abstract
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.
Highlights
Epidermal growth factor (EGF) was discovered by Cohen, and he and his colleagues subsequently extended our knowledge of the mechanisms of action of EGF and its receptor epidermal growth factor receptor (EGFR) [1]
EGFR is a 170 kDa membrane glycoprotein, which is activated by ligands such as EGF, transforming growth factor (TGF)-α, heparin-binding EGF, amphiregulin, betacellulin, and epiregulin
These proteins are synthesized as transmembrane precursors and are cleaved proteolytically by metalloproteases to release the mature growth factor, which can interact with EGFR and cause its activation
Summary
Epidermal growth factor (EGF) was discovered by Cohen, and he and his colleagues subsequently extended our knowledge of the mechanisms of action of EGF and its receptor EGFR [1]. Neutrophil infiltration in airways is characteristic of patients with COPD, and activated neutrophils increase EGFR tyrosine phosphorylation and subsequent MUC5AC expression at both the mRNA and protein levels in NCI-H292 cells These effects can be blocked by selective EGFR inhibitors. These findings implicate neutrophils and TNF-α in wound-induced EGFR activation and goblet-cell metaplasia These studies show the importance of the EGFR cascade in allergic mucus hypersecretion. Bacterial infection Mucus hypersecretion is characteristic of cystic fibrosis [10], and P. aeruginosa infections are associated with deterioration and death from cystic fibrosis This has led to studies of the effect of Gram-negative bacterial products (including endotoxin) on mucin production; for example, Escherichia coli endotoxin increases epithelial mucosubstances [31], causes goblet-cell metaplasia in rat nose [32], and increases mucin synthesis in the lower airways [33]. Kohri et al [36] reported that selective EGFR inhibitors prevent P. aeruginosa-induced mucin synthesis in human airway epithelial (NCI-H292) cells, again implicating EGFR activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
