Department of Respiratory Sciences, University of Leicester, UK, Institute of Lung Health and NIHR Leicester BRC-Respiratory, Leicester, UK.
Department of Molecular and Cell Biology, University of Leicester, Leicester, UK.
Sci Rep. 2019 Dec 12;9(1):18942. doi: 10.1038/s41598-019-55405-2.
Chronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs.
慢性阻塞性肺疾病（COPD）是发病率和死亡率的主要原因。全基因组关联研究表明，在编码 tensin1 的 TNS1 基因中的非同义 SNP 与气流阻塞或 COPD 之间存在显著关联。然而，tensin1 在人类气道组织和细胞中的表达、细胞分布和功能尚不清楚。因此，我们在对照者和 COPD 或哮喘患者的组织和细胞中检查了这些特征。气道组织用 tensin1 进行免疫染色。使用 qRT-PCR、western blot 和免疫荧光染色评估培养的人气道平滑肌细胞（HASMC）中的 tensin1 表达。使用 siRNA 下调 tensin1 表达。与对照组相比，COPD 组织中的气道平滑肌和固有层中 tensin1 的表达增加，但在哮喘组织中没有增加。tensin1 在 HASMCs 中表达，并被 TGFβ1 上调。TGFβ1 和纤维连接蛋白增加了 tensin1 向纤维状黏附的定位。tensin1 和α-平滑肌肌动蛋白（αSMA）强烈共定位，并且 HASMCs 中 tensin1 的耗竭减弱了两者的αSMA 表达和胶原蛋白凝胶的收缩。总之，tensin1 在 COPD 气道中的表达增加，并且可能通过增强收缩蛋白的表达及其在 HASMCs 中向应激纤维的定位来促进气道阻塞。
