VEGF synthesis is induced by prostacyclin and TGF-β in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling.

Autor: Westergren‐Thorsson, Gunilla, Bagher, Mariam, Andersson‐Sjöland, Annika, Thiman, Lena, Löfdahl, Claes‐Göran, Hallgren, Oskar, Bjermer, Leif, Larsson‐Callerfelt, Anna‐Karin
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Zdroj: Respirology; Jan2018, Vol. 23 Issue 1, p68-75, 8p
Abstrakt: ABSTRACT Background and objective Involvement of pulmonary vascular remodelling is a characteristic sign in COPD. Vascular mediators such as vascular endothelial growth factor ( VEGF) and prostacyclin may regulate fibroblast activity. The objective was to study the synthesis of VEGF and interactions with prostacyclin and transforming growth factor ( TGF)-β1 in lung fibroblasts from patients with COPD and healthy control subjects. To further explore the autocrine role of synthesized VEGF on fibroblast activity, studies were performed in human lung fibroblasts ( HFL-1). Methods Primary distal lung fibroblast cultures were established from healthy individuals and from COPD patients ( GOLD stage IV). Lung fibroblasts were stimulated with the prostacyclin analogue iloprost and the profibrotic stimuli TGF-β1. VEGF synthesis was measured in the cell culture medium. Changes in proliferation rate, migration and synthesis of the extracellular matrix ( ECM) proteins proteoglycans were analysed after stimulations with VEGF-A isoform 165 ( VEGF165; 1-10 000 pg/ mL) in HFL-1. Results Iloprost and TGF-β1 significantly increased VEGF synthesis in both fibroblasts from COPD patients and control subjects. TGF-β1-induced VEGF synthesis was significantly reduced by the cyclooxygenase inhibitor indomethacin in fibroblasts from COPD patients. VEGF significantly increased proliferation rate and migration capacity in HFL-1. VEGF also significantly increased synthesis of the ECM proteins biglycan and perlecan. The VEGF receptors ( VEGFR), VEGFR1, VEGFR2 and VEGFR3, were all expressed in primary lung fibroblasts and HFL-1. Conclusion VEGF is synthesized in high amounts by distal lung fibroblasts and may have a crucial role in ongoing vascular remodelling processes in the distal lung compartments. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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