Nakao Atsuhito, Sagara Hironori, Setoguchi Yasuhiro, Okada Takenori, Okumura Ko, Ogawa Hideoki, Fukuda Takeshi
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
J Allergy Clin Immunol. 2002 Dec;110(6):873-8. doi: 10.1067/mai.2002.129236.
Smad7 is an intracellular antagonist of transforming growth factor beta (TGF-beta) signaling, which could determine the intensity or duration of the TGF-beta signal. Because TGF-beta has been implicated in the development of airway remodeling in asthma on the basis of its strong capacity to induce extracellular matrix production, it is possible that Smad7 also plays some roles in the regulation of the process.
We sought to determine the relationships between Smad7 expression in bronchial biopsy samples from asthmatic subjects and clinicopathologic features.
Bronchial biopsy specimens were obtained from 40 asthmatic subjects and 6 healthy control subjects. Expression levels of Smad7 on a histologic section were estimated by immunohistochemical staining. In addition, the roles of Smad7 in TGF-beta-mediated transcriptional responses were studied by in vitro studies.
Smad7 immunoreactivity was detected mainly in bronchial epithelial cells in control and asthmatic subjects. Interestingly, asthmatic subjects exhibited less Smad7 immunoreactivity in bronchial epithelial cells than normal subjects. Expression levels of Smad7 in bronchial epithelial cells were inversely correlated with basement membrane thickness and airway hyperresponsiveness in asthmatic subjects. In addition, abrogation of endogenous Smad7 expression through use of an antisense oligonucleotide enhanced transcriptional responses to TGF-beta, whereas overexpression of Smad7 inhibited TGF-beta-induced plasminogen activator inhibitor 1production in a human bronchial epithelial cell line, BEAS2B cells.
These findings suggest that Smad7 is a key molecule that defines the susceptibility of bronchial epithelial cells to TGF-beta action and that regulation of Smad7 expression in bronchial epithelial cells might be related to the development of airway remodeling and airway hyperresponsiveness in asthma.
Smad7是转化生长因子β（TGF-β）信号通路的细胞内拮抗剂，可决定TGF-β信号的强度或持续时间。由于TGF-β具有强大的诱导细胞外基质产生的能力，已被认为与哮喘气道重塑的发生有关，因此Smad7可能也在该过程的调节中发挥一定作用。
我们试图确定哮喘患者支气管活检样本中Smad7表达与临床病理特征之间的关系。
从40例哮喘患者和6例健康对照者获取支气管活检标本。通过免疫组织化学染色评估组织切片上Smad7的表达水平。此外，通过体外研究探讨Smad7在TGF-β介导的转录反应中的作用。
在对照者和哮喘患者中，Smad7免疫反应性主要在支气管上皮细胞中检测到。有趣的是，哮喘患者支气管上皮细胞中的Smad7免疫反应性低于正常受试者。哮喘患者支气管上皮细胞中Smad7的表达水平与基底膜厚度和气道高反应性呈负相关。此外，使用反义寡核苷酸消除内源性Smad7表达可增强对TGF-β的转录反应，而Smad7的过表达则抑制人支气管上皮细胞系BEAS2B细胞中TGF-β诱导的纤溶酶原激活物抑制剂1的产生。
这些发现表明，Smad7是决定支气管上皮细胞对TGF-β作用易感性的关键分子，支气管上皮细胞中Smad7表达的调节可能与哮喘气道重塑和气道高反应性的发生有关。
