Abstract OBJECTIVE: To explore the relationship of airway remodeling with epidermal growth factor receptor (EGFR) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) levels in asthmatic mice and the effect of EGFR tyrosine kinase inhibitor (AG1478) on airway remodeling. METHODS: Twenty-four male BALB/c mice were randomly divided into three groups: normal control, asthma, AG1478-treated. Mice were sensitized and challenged with ovalbumin (OVA) and a mouse mode1 of asthma was prepared. Collagen deposition was determined in Masson-stained lung sections. Periodic acid Schiff (PAS) staining was used to observe the proliferation of goblet cells. Immunohistochemistry was used to determine the protein expression of HB-EGF. RT-PCR was used to determine the mRNA expression of HB-EGF and EGFR. RESULTS: The characteristic changes of airway remodeling occurred in the asthma group. The expression of HB-EGF and EGFR in the epithelial cells of bronchi in the asthma group was significantly higher than that in the normal control group. Compared with the asthma group, the AG1478-treated group had decreased inflammation reactions, decreased collagen deposition and proliferation of goblet cells and lower expression of EGFR and HB-EGF. CONCLUSIONS: EGFR tyrosine kinase inhibitor (AG1478) ameliorates the progression of airway remodeling in mice with asthma by inhibitions of EGFR and HB-EGF expression and EGFR signal pathway.［Chin J Contemp Pediatr, 2010, 12 (2):137-140］
LI Xiao-Hui,LUAN Bin. Effect of epidermal growth factor receptor on airway remodeling in asthmatic mice and its mechanism[J]. 中国当代儿科杂志, 2010, 12(2): 137-140.
LI Xiao-Hui,LUAN Bin. Effect of epidermal growth factor receptor on airway remodeling in asthmatic mice and its mechanism[J]. CJCP, 2010, 12(2): 137-140.
［1］ Sumi Y, Hamid Q. Airway remodeling in asthma［J］. Allergol Int, 2007, 56（4）:341-348.
［2］Tamaoka M, Hassan M, McGovern T, RamosBarbon D, Jo T, Yoshizawa Y et al. The epidermal growth factor receptor mediates allergic airway remodeling in the rat ［J］.Eur Respir J, 2008, 32（5）:1213-1223.
［3］Du Q, Chen Z, Zhou LF, Zhang Q, Huang M, Yin KS. Inhibitory effects of astragaloside Ⅳ on ovalbumin-induced chronic experimental asthma［J］. Can J Physiol Pharmacol, 2008, 86(7):449-457.
［4］Puddicombe SM, Polosa R, Richter A, Krishna MT, Howarth PH, Holgate ST, Davies DE. Involvement of the epidermal growth factor receptor in epithelial repair in asthma［J］.FASEB J, 2000(7), 14:1362-1374.
［5］Hamilton LM, Puddicombe SM, Dearman RJ, Kimber I, Sandstro¨m T, Wallin A et al. Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium［J］.Eur Respir J, 2005, 25(6):978-985.
［6］Fedorov IA, Wilson SJ, Davies DE, Holgate ST. Epithelial stress and structural remodelling in childhood asthma［J］.Thorax, 2005, 60（10）:389-394.
［7］Ellis AG, Nice EC, Weinstock J.Hish-performance liquid chromatographic an alysis of the tyrphostin AG1478, a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in mouse plasma［J］．Chromatogr B Biomed Sci, 2001, 754(1): 193-199.
［8］Busse D, Doughty RS, Ramsey TT, Russell WE, Price JO, Flanagan WM et al. Reversible G1 arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27 Kip1 independent of MAPK activity［J］. J Biol Chem, 2000, 275(10): 6987-6995.
［9］Vargaftig BB, Singer M. Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR［J］. Am J Physiol Lung Cell Mol Physiol, 2003, 285(6):L808-L818.
