Irisin stimulates the secretion of hyaluronic acid by airway smooth muscle cells from patients with chronic obstructive pulmonary disease

Abstract

Irisin is a recently discovered myokine, which has been proposed to mediate the beneficial effects of exercise as it increases total body energy expenditure, reduces body weight and increases insulin sensitivity. Physical activity has been emphasized as one of the principal targets for the treatment of COPD. Hyaluronic acid (HA) plays a key role in airway remodeling, which is a hallmark in COPD. The aim of our study was to investigate the effect of irisin on the secretion of HA by primary human airway smooth muscle cells (ASMC) from patients with COPD. We established primary cultures of ASMC from endo-bronchial biopsies of patients with COPD. Cells were stimulated with irisin (1-40 nM) and the secretion of HA was measured by ELISA. The expression of HA synthases (HAS) 1, 2 and 3, hyaluronidases (HYAL) 1, 2 and 3 and HA receptors CD44 and RHAMM (receptor for HA-mediated motility) was investigated by real-time PCR. Irisin stimulated the secretion of HA by ASMC in a time- and dose-dependent manner. This effect became significant (p In conclusion, these results indicate that irisin is involved in the turnover of HA in the airways of patients with COPD by targeting HA metabolizing enzymes. Thus, irisin may be proved as a new pharmacological target to control airway remodeling in COPD.