Abstract
Background: Physical activity is a principal target in the treatment of chronic obstructive pulmonary disease (COPD). Irisin, a recently identified myokine, has been controversially associated chronic exercise.
Aims and objectives: To clarify the role of irisin in COPD and its interaction with hyaluronic acid (HA), a glycosaminoglycan that plays a key role in airway remodeling in COPD.
Methods: We used primary airway smooth muscle cells (ASMC) and fibroblasts from patients with COPD, and skeletal muscle cells that are known to produce irisin, as controls. Cells were stimulated with irisin and secreted HA was measured by ELISA. We also assessed irisin and HA serum levels in 638 patients with stable COPD, GOLD II-IV, >10 PY, included in the PROMISE cohort. The primary outcome of the study was exacerbation and/or death. Median observation time was 24 months.
Results: Irisin stimulates significantly (p<0.001) in a time- and dose-dependent manner the secretion of HA by ASMC and SkMC, but not by fibroblasts. There was a significant (p=0.002) correlation (rho=0.142) between HA and irisin serum levels in COPD patients. Circulating irisin was higher in patients with severe exacerbations as compared with patients without severe exacerbations (1480 ± 121 μg/ml vs 1265 ± 88 μg/ml p=0.009). HA was associated significantly (p<0.001) with time to death (Exp(B) 1.019 95% CI 1.009-1.029), while irisin was associated significantly (p=0.004) with the number of severe exacerbations per year (OR 0.134 95% CI 0.051-0.269).
Conclusions: Our results indicate that irisin stimulates HA secretion, in a cell-specific way, and this is associated with COPD progression and severity.
- Copyright ©the authors 2016