Inhibition of nerve growth factor/tyrosine kinase receptor A signaling ameliorates airway remodeling in chronic allergic airway inflammation

L.-W. Huang, G. Sun, D.-L. Wang, L.-F. Kong

Institute of Respiratory Diseases, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, P.R. China. lingfeikong1234@163.com

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• Respiratory Medicine

OBJECTIVE: The molecular mechanism leading to airway remodeling in patients with allergic asthma is not fully understood. We determined the role of nerve growth factor/tyrosine kinase receptor A signaling in airway remodeling in chronic allergic airway inflammation, and proved that inhibited nerve growth factor (NGF) production ameliorates airway remodeling during chronic allergic airway inflammation.

MATERIALS AND METHODS: Six- to eight-week-old female BALB/c mice were used in this study. Mice were randomized into four groups: phosphate buffer saline (PBS) control group (n = 10); chronic asthmatic group (n = 12); anti-NGF group (n=12); and anti-TrkA group (n=12). First, to determine the impact of NGF on airway remodeling, antibody-blocking experiments were performed in a chronic allergic murine model characterized by matrix deposition in the subepithelial. Secondly, the number of eosinophils, macrophages, neutrophils and the total number of cells in bronchoalveolar lavage fluid (BALF) was counted. Thirdly, growth-associated protein 43 (GAP43) and NGF protein expression was measured by western blot.

RESULTS: It was shown that the number of eosinophils and the total inflammatory cells, NGF and GAP43 protein expression in BALF were markedly higher in asthma group, compared to the other groups. And given anti-NGF or anti-TrkA antibody treatment can reduced GAP43 expression and collagen deposition in the airway.

CONCLUSIONS: NGF triggers wound healing process and airway remodeling by inducing GAP43 production dependent on TrkA in a mouse model of chronic experimental asthma. Controlling epithelial NGF production might be an efficient therapeutic target to prevent allergic asthma.

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