Unit of Lung Biology, Department of Experimental Medical Sciences, BMC D12, Lund University, Lund 221 84, Sweden.
Respir Res. 2013 Feb 14;14(1):21. doi: 10.1186/1465-9921-14-21.
Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM) in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin.
Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV) and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts.
TGF-β1 stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p < 0.01), but showed no effect on fibroblasts from control subjects. Collagen I synthesis was decreased by iloprost in both control and COPD fibroblasts (p < 0.05). Conversely, iloprost significantly altered biglycan and decorin synthesis in control fibroblasts, but iloprost displayed no effect on these proteoglycans in COPD fibroblasts. Proliferation rate was reduced (p < 0.05) and contractile capacity was increased in COPD fibroblasts (p < 0.05) compared to control fibroblasts. Iloprost decreased proliferative rate in control fibroblasts (p < 0.05), whereas iloprost attenuated contraction capacity in both COPD (p < 0.01) and control fibroblasts (p < 0.05).
Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients.
前列环素类似物是强效的血管扩张剂，具有抗炎特性。然而，前列环素对 COPD 中细胞外基质（ECM）的影响尚不清楚。胶原纤维和蛋白聚糖是肺中 ECM 的重要组成部分，成纤维细胞是调节 ECM 蛋白平衡的关键因素。目的是研究前列环素的合成及其对成纤维细胞活性和 ECM 产生的影响，特别是胶原 I 以及胶原相关蛋白聚糖 biglycan 和 decorin。
从 COPD 患者（GOLD 分期 IV 期）的肺部以及对照受试者的肺部和经支气管活检中分离出肺实质成纤维细胞。使用前列环素类似物伊洛前列素来研究前列环素对 ECM 蛋白合成、成纤维细胞迁移、增殖和收缩能力的影响。
TGF-β1 刺激显著增加了 COPD 患者成纤维细胞中的前列环素合成（p<0.01），但对对照受试者的成纤维细胞没有影响。伊洛前列素降低了对照和 COPD 成纤维细胞中的胶原 I 合成（p<0.05）。相反，伊洛前列素显著改变了对照成纤维细胞中的 biglycan 和 decorin 合成，但伊洛前列素对 COPD 成纤维细胞中的这些蛋白聚糖没有影响。与对照成纤维细胞相比，COPD 成纤维细胞的增殖率降低（p<0.05），收缩能力增强（p<0.05）。伊洛前列素降低了对照成纤维细胞的增殖率（p<0.05），而伊洛前列素减弱了 COPD（p<0.01）和对照成纤维细胞（p<0.05）的收缩能力。
伊洛前列素降低了胶原 I 合成和成纤维细胞的收缩能力，但对 COPD 患者成纤维细胞中的胶原相关蛋白聚糖或增殖率没有影响。前列环素生成增加可能导致严重 COPD 患者胶原网络纤维生成异常和肺气肿结构更严重。
