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.

几种细胞因子已被认为在支气管哮喘气道重塑中发挥重要作用，一种新克隆的生长因子，即结缔组织生长因子（CTGF），已被阐明在纤维化中发挥直接的TGF-β作用。通过对支气管组织标本、培养的人支气管上皮细胞和实验鼠模型肺组织的分析，评价CTGF在气道重塑中的作用。 1．哮喘反复暴露于雾化卵清蛋白后，分析了卵清蛋白致敏小鼠肺中CTGF表达与上皮下纤维化之间的关系。结果：在反复吸入激发后，观察到支气管上皮中明显的杯状细胞增生和上皮下粘膜中过度的胶原沉积。卵清蛋白攻击小鼠肺组织中的 β2 水平在第 7 天和第 14 天升高与暴露于盐水的小鼠相比，CTGF的免疫组织化学显示，在卵清蛋白吸入激发后第7天和第14天，支气管粘膜下层中的CTGF阳性细胞增加。2． ：CTGF mRNA 的 RT-PCR 表明嗜酸性粒细胞和气道上皮细胞均表达 CTGF 基因。 CTGF免疫组化显示，与正常人相比，哮喘患者支气管粘膜下层中CTGF阳性细胞增多，且支气管粘膜下层CTGF阳性细胞数量与基底膜厚度显着相关。结论：CTGF是TGF的下游介质。 -β在哮喘患者的支气管粘膜下层中高表达，可能在气道重塑中发挥作用。

项目成果

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