Airway smooth muscle malfunction in COPD

Airway smooth muscle has been conventionally regarded as a contractile partner in bronchoconstriction. It also interacts dynamically with its environment, especially under inflammatory conditions, modulates the pathological processes in the development of chronic obstructive pulmonary disease (COPD). Airway smooth muscle cells are able to proliferate, to secrete cytokines, growth factors, prostanoid, and extracellular matrix proteins, and to adapt to these functions by changing its phenotype from contractile to synthetic. In COPD, smooth muscle in the small airways exhibit hyperresponsiveness and higher contractility in calcium-dependent and -independent mechanisms. Airway smooth muscle cell hyperplasia and hypertrophy as well as increased deposition of extracellular matrix (ECM) proteins contribute to airway remodeling and thickening. Many inflammatory mediators and growth factors, including interleukins, tumor necrosis factor-α (TNF-α), leukotrienes, prostaglandins, acetylcholine, platelet-derived growth factor (PDGF), transform growth factor β (TGFβ), connective tissue growth factor (CTGF), endothelin, and reactive oxygen species (ROS), contribute to the alterations of airway smooth muscle in COPD. Investigating the mechanism and regulatory pathways of airway smooth muscle malfunction may provide novel options for the prevention and treatment for airflow obstruction in COPD.