Sagara Hironori, Okada Takanori, Okumura Ko, Ogawa Hideoki, Ra Chisei, Fukuda Takeshi, Nakao Atsuhito
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan.
J Allergy Clin Immunol. 2002 Aug;110(2):249-54. doi: 10.1067/mai.2002.126078.
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.
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.
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.
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.
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.
有研究表明,转化生长因子β(TGF-β)在哮喘气道重塑的发生发展中起重要作用;这一观点基于TGF-β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,相关研究尚无定论,因为它们无法证明该细胞因子在哮喘患者气道中介导的活性信号传导。
我们试图确定TGF-β信号传导在哮喘患者气道中是否活跃,如果活跃,它是否与哮喘气道重塑发生发展相关的临床病理特征相关。
我们检测了40例哮喘患者支气管活检样本中Smad2的磷酸化状态,以此作为TGF-β活性信号的标志物,并研究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Smad2的表达水平高于正常受试者标本,且与哮喘患者的基底膜厚度相关。
这些发现提供了证据,表明TGF-β信号传导在哮喘气道中是活跃的,且这种活性与哮喘气道重塑的发生发展相关。