细胞外基质(ECM)重塑与慢性阻塞性肺疾病(COPD)的气道不可逆阻塞和肺泡组织破坏有关。调查COPD肺ECM差异的研究主要集中在一些胶原蛋白和弹性蛋白,留下一系列未被探索的ECM组件。我们调查了ECM景观的差异,比较重度早期发作(SEO-)COPD和中度COPD与I型胶原α链1(COL1A1)的对照肺组织,COL6A1,COL6A2,COL14A1,腓骨蛋白2和5(FBLN2,FBLN5),潜伏转化生长因子-β结合蛋白4(LTBP4),Lumican(LUM),versican(VCAN),decorin(DCN),和弹性蛋白(ELN)使用图像分析和统计建模。LUM在实质中表达的百分比面积和/或平均强度,和COL1A1,FBLN2,LTBP4,DCN,和气道壁中的VCAN,与对照组相比,COPD的比例较低。大多数ECM蛋白水平的降低与FEV1测量值的降低有关,表明与疾病严重程度的关系。此外,我们确定了六个独特的ECM特征,其中在薄壁组织中LUM和COL6A1,以及COL1A1,FBLN5,DCN,气道壁中的VCAN在反映COPD的存在和严重程度方面似乎是必不可少的。这些特征强调需要检查蛋白质组以代表COPD中ECM景观的总体差异。更有可能与功能效应有关,比单个蛋白质。我们的研究揭示了对照组和COPD之间以及SEO和中度COPD之间的肺ECM景观差异,表明不同亚组的不同病理过程。
Extracellular matrix (ECM) remodeling has been implicated in the irreversible obstruction of airways and destruction of alveolar tissue in chronic obstructive pulmonary disease (COPD). Studies investigating differences in the lung ECM in COPD have mainly focused on some collagens and elastin, leaving an array of ECM components unexplored. We investigated the differences in the ECM landscape comparing severe-early onset (SEO)-COPD and moderate COPD to control lung tissue for collagen type I α chain 1 (COL1A1), collagen type VI α chain 1 (COL6A1); collagen type VI α chain 2 (COL6A2), collagen type XIV α chain 1 (COL14A1), fibulin 2 and 5 (FBLN2 and FBLN5), latent transforming growth factor β binding protein 4 (LTBP4), lumican (LUM), versican (VCAN), decorin (DCN), and elastin (ELN) using image analysis and statistical modeling. Percentage area and/or mean intensity of expression of LUM in the parenchyma, and COL1A1, FBLN2, LTBP4, DCN, and VCAN in the airway walls, was proportionally lower in COPD compared to controls. Lowered levels of most ECM proteins were associated with decreasing forced expiratory volume in 1 s (FEV1) measurements, indicating a relationship with disease severity. Furthermore, we identified six unique ECM signatures where LUM and COL6A1 in parenchyma and COL1A1, FBLN5, DCN, and VCAN in airway walls appear essential in reflecting the presence and severity of COPD. These signatures emphasize the need to examine groups of proteins to represent an overall difference in the ECM landscape in COPD that are more likely to be related to functional effects than individual proteins. Our study revealed differences in the lung ECM landscape between control and COPD and between SEO and moderate COPD signifying distinct pathological processes in the different subgroups.NEW & NOTEWORTHY Our study identified chronic obstructive pulmonary disease (COPD)-associated differences in the lung extracellular matrix (ECM) composition. We highlight the compartmental differences in the ECM landscape in different subtypes of COPD. The most prominent differences were observed for severe-early onset COPD. Moreover, we identified unique ECM signatures that describe airway walls and parenchyma providing insight into the intertwined nature and complexity of ECM changes in COPD that together drive ECM remodeling and may contribute to disease pathogenesis.