Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease
- Authors
- Shim J.J.
- Issue Date
- 2003
- Publisher
- Korean National Tuberculosis Association
- Keywords
- Airway; Cell signal; Epidermal growth factor; G-protein; Mucin production
- Citation
- Tuberculosis and Respiratory Diseases, v.55, no.1, pp 21 - 30
- Pages
- 10
- Indexed
- SCOPUS
- Journal Title
- Tuberculosis and Respiratory Diseases
- Volume
- 55
- Number
- 1
- Start Page
- 21
- End Page
- 30
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/32419
- DOI
- 10.4046/trd.2003.55.1.21
- ISSN
- 0378-0066
- Abstract
- Background: Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method: MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, TNF α was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNF α antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results: LPS alone did not increase significantly MUC5AC production. LPS with TGF α induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNF α secretion, which was inhibited by mastoparan. LPS with TGF α-induced MUC5AC production was inhibited by neutralizing polyclonal TNF a antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion: In LPS-induced MUC5AC synthesis, LPS causes TNF a secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.
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Collections - 2. Clinical Science > Department of Pulmonary, Allergy, and Critical Care Medicine > 1. Journal Articles
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