Late Breaking Abstract - Hypoxia-induced cellular responses in lung fibroblasts from COPD patients and controls

Background: COPD is a heterogeneous disease with limited pulmonary gas exchange that causes hypoxic regions within the lungs which can lead to remodelling. Fibroblasts are major producers of extracellular matrix proteins, angiogenic and remodelling mediators. Objective: The aims were to investigate how distal lung fibroblasts respond to a hypoxic condition and if a hypoxic state triggers similar events that are observed in COPD pathology. Methods: Distally-derived primary lung fibroblasts from non-smokers, smokers and patients with COPD, stage GOLD II and IV (n=3 in each group) were cultured in hypoxic (1% O2) or normoxic conditions for 4 h and 24 h. RT-qPCR, ELISA and immunostaining were performed to analyse the expression of genes and proteins associated with hypoxia, oxidative stress, remodelling and inflammatory responses. Results: Changes were observed in mRNA expression and proteins involved in oxidative, endoplasmic reticulum and mitochondrial stress responses, as well as remodelling and inflammatory mediators from fibroblasts from COPD patients compared to healthy subjects (smokers and non-smokers) in response to hypoxia. Heterogeneity in expressions was observed within the groups. Release of VEGF-C increased during hypoxia in fibroblasts from patients with GOLD II (p<0.05) and decreased in patients with GOLD IV compared to healthy subjects. Release of PGF1α and PGE2 were increased (p<0.05) in fibroblasts from patients with GOLD II compared to healthy subjects, both at normoxia and hypoxia. Conclusions: Our data provides insights into the altered activity of fibroblasts in COPD pathology and how a hypoxic condition may alter cellular activity that can lead to improved treatment options.