Role of connective tissue growth factor (CTGF) in airway remodeling in asthma

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Several cytokines have been recognized to play important roles in airway remodeling in bronchial asthma. A newly cloned growth factor, connective tissue growth factor (CTGF), has been elucidated to play a direct role of TGF-β action in fibrosis. Present study was designed to evaluate a role of CTGF in airway remodeling by analysis on bronchial tissue specimen, cultured human bronchial epithelial cells and lung tissue of experimental murine model.1. Study on experimental murine model with asthmaRelationship between CTGF expression and subepithelial fibrosis was analyzed in lung of ovalbuminsensitized mice after repetitive exposure to aerosolized ovalbumin.Result : After repetitive inhalation challenge, prominent goblet cell hyperplasia in bronchial epithelium and exaggerated collagen deposition in subepithelial mucosa were observed. The levels of CTGF mRNA in pulmonary tissue of ovalbumin challenged mice were elevated on 7th day and 14th day compared to mice exposed saline. Immunohistochemistry for CTGF revealed that CTGF positive cells increased in bronchial submucosa on 7^<th> day and l4^<th> day after ovalbumin inhalation challenge.2. Study on bronchial biopsy specimen from patients with bronchial asthmaResult : RT-PCR for CTGF mRNA demonstrated that both eosinophils and airway epithelial cells express CTGF gene. Immunohistochemistry for CTGF revealed that CTGF positive cells increased in bronchial submucosa of patients with asthma, compared to normal subjects. Furthermore, the number of CTGF positive cells in bronchial submucosa correlated with thickness of basement membrane significantly.Conclusion : CTGF, a downstream mediator of TGF-β, is highly expressed in bronchial submucosa of patients with asthma and may play a role in airway remodeling.