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

一些细胞因子已被认为在哮喘的气道重塑中起重要作用。结缔组织生长因子是新近克隆的一种生长因子，它直接参与转化生长因子-β在肝纤维化中的作用。本研究旨在通过对支气管组织标本、培养的人支气管上皮细胞和实验性小鼠肺组织的分析，探讨CTGF在气道重塑中的作用。反复雾化吸入卵白蛋白致敏小鼠肺组织CTGF表达与上皮下纤维化的关系。结果：反复吸入激发后，小鼠支气管上皮细胞杯状细胞明显增生，上皮下胶原沉积增多。与生理盐水组相比，卵蛋白攻击后第7天和第14天小鼠肺组织中CTGF mRNA的表达水平升高。结果：1.免疫组织化学显示，吸入卵蛋白后第7天和第14天，支气管粘膜下层CTGF阳性细胞明显增多。结果：逆转录聚合酶链式反应显示嗜酸性粒细胞和呼吸道上皮细胞均表达CTGF基因。CTGF免疫组织化学结果显示，哮喘患者支气管黏膜下层CTGF阳性细胞较正常人明显增多。结论：转化生长因子-β的下游介导物CTGF在哮喘患者的支气管黏膜下层高表达，可能参与了哮喘的气道重塑。

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.