β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction.
β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction.
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DOI：
10.1038/s41598-017-11375-x
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发表时间：
2017-09-07
影响因子：
4.6
通讯作者：
Sohal SS
中科院分区：
文献类型：
--
作者：
Mahmood MQ;Walters EH;Shukla SD;Weston S;Muller HK;Ward C;Sohal SS
慢性阻塞性肺病的特点是可逆性较差的气流阻塞，通常由吸烟引起。转录因子簇β-catenin/Snail1/Twist与上皮间充质转化（EMT）过程有关，EMT是吸烟和气道纤维化之间的中介，实际上是肺癌。我们研究了这些转录因子的表达及其“细胞定位”在COPD患者的支气管镜气道活检中，以及吸烟和不吸烟的对照组中。免疫组织化学研究比较了这些受试者在3个大气道腔室(上皮（基底区）、网状基底膜（Rbm）和下固有层（LP）中β-catenin、Snail1和Twist的细胞蛋白表达。β-catenin和Snail1在COPD患者气道壁的表达普遍较高，且有明显的细胞质向核转移（P < 0.01）。正常组Twist在上皮中普遍表达，吸烟组Twist在基底和细胞核中表达增多（P < 0.05）。此外，β-catenin和Snail1的表达，以及Twist的较小程度，与气流阻塞和典型EMT生物标志物（S100A4）的表达有关。β-catenin-Snail1-Twist转录因子簇在吸烟者和COPD中表达上调和核易位，其表达与EMT活性和气道阻塞密切相关。
COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer. We have investigated expression of these transcription factors and their “cellular localization” in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01). Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05). In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4). The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction.
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