Defective alterations in the collagen network to prostacyclin in COPD lung fibroblasts

Abstract

Abstract Background 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. Methods 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. Results TGF-β1 stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p Conclusions 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.

Keywords

• Chronic obstructive pulmonary disease
• Collagen I
• Fibroblast
• Prostacyclin
• Proteoglycans
• Decorin
• Biglycan
• Proliferation
• Fibroblast gel contraction
• Transforming growth factor β