Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: the role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates procellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Revisiting Skeletal Muscle Dysfunction and Exercise in Chronic Obstructive Pulmonary Disease: Emerging Significance of Myokines.

Skeletal muscle dysfunction (SMD) is the most significant extrapulmonary complication and an independent prognostic indicator in patients with chronic obstructive pulmonary disease (COPD). Myokines, such as interleukin (IL)-6, IL-15, myostatin, irisin, and insulin-like growth factor (IGF)-1, play important roles in skeletal muscle mitochondrial function, protein synthesis and breakdown balance, and regeneration of skeletal muscles in COPD. As the main component of pulmonary rehabilitation, exercise can improve muscle strength, muscle endurance, and exercise capacity in patients with COPD, as well as improve the prognosis of SMD and COPD by regulating the expression levels of myokines. The mechanisms by which exercise regulates myokine levels are related to microRNAs. IGF-1 expression is upregulated by decreasing the expression of miR-1 or miR-29b. Myostatin downregulation and irisin upregulation are associated with increased miR-27a expression and decreased miR-696 expression, respectively. These findings suggest that myokines are potential targets for the prevention and treatment of SMD in COPD. A comprehensive analysis of the role and regulatory mechanisms of myokines can facilitate the development of new exercise-based therapeutic approaches for patients with COPD.