Department of Experimental Medical Science, BMC D12 Lund, Lund University, Sweden.
Respir Res. 2010 May 11;11(1):55. doi: 10.1186/1465-9921-11-55.
Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production.
Proliferation, proteoglycan production and the response to TGF-beta1 were examined in vitro in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects.
Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p < 0.01). In addition, perlecan production was lower in centrally derived fibroblasts from COPD patients than from control subjects (p < 0.01). TGF-beta1 triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-beta1 than those from control subjects.
The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD.
COPD 中的气道重塑包括细胞外基质的重组。蛋白聚糖在这个过程中作为细胞外基质完整性的调节剂起着至关重要的作用。在 COPD 肺中已经证明了蛋白聚糖免疫染色的改变，并且这被认为有助于发病机制。负责产生和维持 ECM 成分（如蛋白聚糖）的主要细胞类型是成纤维细胞。有趣的是，有人提出中央气道和肺泡肺实质包含不同的成纤维细胞群体。这项研究探讨了这样一种假设，即在 COPD 肺中，特别是在 versican 和 perlecan 中，改变的蛋白聚糖沉积是由于成纤维细胞蛋白聚糖产生失调的结果。
在体外研究了从 COPD 患者（GOLD 阶段 IV）和对照受试者中分离的中央和远端衍生的成纤维细胞中的增殖、蛋白聚糖产生和对 TGF-β1 的反应。
在中央气道和肺实质中鉴定出表型不同的成纤维细胞群体。来自 COPD 患者的远端成纤维细胞的 versican 产生高于对照组（p < 0.01）。此外，来自 COPD 患者的中央衍生成纤维细胞的 perlecan 产生低于对照组（p < 0.01）。TGF-β1 引发来自 COPD 患者和对照组的远端衍生成纤维细胞中类似的蛋白聚糖产生增加。相比之下，来自 COPD 患者的中央衍生成纤维细胞对 TGF-β1的反应性低于对照组。
结果表明，COPD 患者的成纤维细胞在蛋白聚糖产生方面存在改变，这可能有助于疾病的发展。来自 COPD 患者的远端衍生成纤维细胞具有增强的 versican 产生，这可能对弹性回缩产生负面影响。此外，来自 COPD 患者的中央衍生成纤维细胞中 perlecan 产生较低可能表明严重 COPD 中支气管基底膜完整性的改变。
