Background: Skeletal muscle dysfunction is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Airway epithelium cells dysfunction involved into systemic inflammation. Airway epithelium cells dysfunction involved into systemic inflammation. The current study attempted to clarify whether and how small extracellular vesicles (sEV) may mediate pathological communication between dysfunctional airway epithelium cells and skeletal muscle cells during COPD.

Methods: Mice were exposed to CS for 12 weeks. sEV (from plasma of patients or mice, or CS-challenged airway epithelium cells) were injected intramuscular or treat with primary skeletal muscle cells.

Results: Increased plasma sEVs counts in patients with COPD are significantly associated with impaired skeletal muscle function, and could induced skeletal muscle cells dysfunction in vivo and in vitro. Next, plasma sEVs from patients with COPD or CS-injured airway epithelial cell induce skeletal muscle cell atrophy in vivo and in virto. Finally, we identified miR-142-3p as the most important molecule of sEVs mediating pro-skeletal muscle dysfunction in airway epithelial cells of COPD. Intramuscular injection of miR-142-3p mimic significantly increased skeletal muscle dysfunction in non-COPD muscle, miR-142-3p inhibitor administrations significantly attenuated skeletal muscle dysfunction in COPD.

Conclusion: miR-142-3p enrichment in dysfunctional airway epithelial cell-derived sEV, is a novel mechanism inducing skeletal muscle dysfunction.