UC San Diego

Chronic smokers present lower limb muscle dysfunction prior to the onset of overt respiratory limitations. Skeletal muscle dysfunction induced by cigarette smoke (CS) includes muscle weakness, loss of muscle mass, and decreased fatigue resistance, which directly lead to exercise intolerance. Smokers and those who develop COPD have higher incidence of muscle injury and show poor muscle regenerative capacity. The mechanism by which muscle regeneration may be affected following injury in chronic smokers is not well investigated. Therefore, we hypothesized that chronic CS exposure delays the trajectory of muscle regeneration following an eccentric exercise-induced muscle injury (EEIMI). We aim to investigate the consequences of short- (2 month) and long- (4 month) term CS exposure in mice on muscle regeneration following EEIMI via lengthening contraction procedure (LCP). Our investigation evaluated changes in ex-vivo force contractility, myofiber cross-sectional area (CSA), and the presence of central nucleated myofibers (CNM) 7 days following LCP, during the muscle reconstruction phase. We found the CS exposure leads to a small decrease in EDL force production, a reduction in myofiber CSA, and increase of CNM in injured legs, suggesting regeneration is delayed. We aimed further to investigate the time course of muscle satellite cell (SC) fusion during the regenerative process in Pax7CreERTdTomato mice to understand better the extent of damage induced by the LCP in the TA and EDL muscles. SC fusion was only detected after 5 days recovery in TA and EDL. Together, the data suggest that CS exposure delays early stages of muscle regeneration process.