Activation of TGF-β/Smad2 signaling is associated with airway remodeling in asthma
Activation of TGF-β/Smad2 signaling is associated with airway remodeling in asthma
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DOI：
10.1067/mai.2002.126078
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发表时间：
2002-08-01
影响因子：
14.2
通讯作者：
Nakao, A
中科院分区：
文献类型：
--
作者：
Sagara, H;Okada, T;Nakao, A
工作背景：转化生长因子β（TGF-β）已被认为在哮喘气道重塑的发展中发挥重要作用;这一建议是基于TGF-β的表达水平与气道重塑的独特参数（如基底膜厚度）相关的证据。然而，相关的研究是不确定的，因为他们不能证明在哮喘个体的气道中由细胞因子介导的活性信号传导。目的：我们试图确定TGF-β信号传导是否在哮喘受试者的气道中是活跃的，如果是这样，它是否与哮喘气道重塑的发展相关的临床病理特征相关。我们检测了40名哮喘患者支气管活检样本中Smad 2的磷酸化状态，作为活性TGF-β信号传导的标志物，并研究了其与基底膜厚度的相关性。哮喘患者支气管活检标本中磷酸化Smad 2的表达水平高于正常人，结论：TGF-β信号在哮喘气道中活跃，并与哮喘气道重塑有关。
Background: Transforming growth factor beta (TGF-beta) has been suggested to play an important role in the development of airway remodeling in asthma; this suggestion is based on evidence that expression levels of TGF-beta are correlated with unique parameters of airway remodeling, such as thickness of basement membrane. However, the relevant studies were inconclusive because they were unable to demonstrate active signaling mediated by the cytokine in the airways of asthmatic individuals.Objective: We sought to determine whether TGF-beta signaling was active in the airways of asthmatic subjects and, if so, whether it was correlated with clinicopathologic features associated with the development of airway remodeling in asthma.Methods: We examined the phosphorylation status of Smad2 in bronchial biopsy samples obtained from 40 asthmatic subjects as a marker of active TGF-beta signaling, and we studied its correlation with basement membrane thickness.Results: Expression levels of phosphorylated Smad2 in bronchial biopsy specimens from asthmatic subjects were higher than those in specimens from normal subjects, and they were correlated with basement membrane thickness in asthma.Conclusion: The findings provide evidence that TGF-beta signaling was active in asthmatic airways and that the activity was associated with the development of airway remodeling in asthma.