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

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 < 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).

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.

• Authors: Anna-Karin Larsson-Callerfelt, Oskar Hallgren, Annika Andersson-Sjöland, Lena Thiman, Johan Björklund, Josefine Kron, Kristian Nihlberg, Leif Bjermer, Claes-Göran Löfdahl, Gunilla Westergren-Thorsson
• Journal: Respiratory research (Respir Res) Vol. 14 Pg. 21 (Feb 14 2013) ISSN: 1465-993X [Electronic] England
• PMID: 23406566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BGN protein, human
• Biglycan
• Collagen Type I
• DCN protein, human
• Decorin
• TGFB1 protein, human
• Transforming Growth Factor beta1
• Epoprostenol
• Iloprost

Topics

• Adult
• Biglycan (metabolism)
• Biopsy
• Case-Control Studies
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Collagen Type I (metabolism)
• Decorin (metabolism)
• Epoprostenol (metabolism)
• Female
• Fibroblasts (drug effects, metabolism, pathology)
• Humans
• Iloprost (pharmacology)
• Lung (drug effects, metabolism, pathology)
• Male
• Phenotype
• Pulmonary Disease, Chronic Obstructive (metabolism, pathology)
• Transforming Growth Factor beta1 (metabolism)
• Young Adult