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

结缔组织生长因子（CTGF）在哮喘气道重塑中的作用

• 批准号: 12670570
• 负责人: YAMAUCHI Kohei
• 金额: $ 2.18万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670570/
• 关键词: asthma; remodeling; growth factor; airway epithelial cell; myoepithelial cell; CTGF; TGF-β; immunostaining; 気道炎症; コラーゲン; 遺伝子発現; サイトカイン

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.

目前研究发现，多种细胞因子在支气管哮喘气道重塑中起重要作用。结缔组织生长因子（CTGF）是一种新克隆的生长因子，它在纤维化过程中直接参与TGF-β的作用。本研究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模型肺组织的分析，探讨CTGF在气道重塑中的作用.实验性哮喘小鼠模型的研究分析了反复吸入雾化卵蛋白后卵蛋白致敏小鼠肺中CTGF表达与上皮下纤维化的关系。结果：反复吸入激发后，支气管上皮杯状细胞明显增生，上皮下粘膜胶原沉积增加。与对照组相比，卵白蛋白攻击组小鼠肺组织CTGF mRNA水平在第7天和第14天均升高。免疫组化结果显示，卵白蛋白刺激后第7天和第14天，大鼠支气管粘膜下层CTGF阳性细胞增多<th><th>.结果：CTGF mRNA的RT-PCR结果显示，嗜酸性粒细胞和气道上皮细胞均表达CTGF基因。CTGF免疫组化结果显示，哮喘患者支气管粘膜下层CTGF阳性细胞明显增多。结论：哮喘患者支气管黏膜下层CTGF表达增高，可能参与气道重塑。

项目成果

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