LAUSR

Cigarette smoke (CS) is considered a major risk factor for chronic obstructive pulmonary disease (COPD), which is currently the third leading cause of death in the United States. Studies have indicated that COPD patients have elevated blood low-density lipoprotein (LDL) levels are which may contribute to dysregulation of lipid metabolism. Accumulating data show that miRNAs are involved in various human diseases. However, the role of miRNAs in the pathogenesis of COPD remains poorly defined. In this study, we found that miR-103a expression was significantly reduced in alveolar macrophage (AM) from smokers and COPD patients versus that in AM from non-smokers. Our data indicated that reactive oxygen species (ROS) negatively regulate miR-103a in macrophages. Functionally, miR-103a modulates the expressions of genes involved in lipid metabolism and directly targets LDL receptor (LDLR) in macrophages. Furthermore, overexpression of miR-103a suppressed the accumulation of lipid droplets and reduced the ROS level in macrophages both in vitro and in vivo. Taken together, our findings indicate that downregulation of miR-103a contributes to CS-induced lipid-laden macrophage formation and plays a critical role in lipid homeostasis in lung macrophages in the pathogenesis of COPD.