Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia.
Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Saudi Arabia.
Am J Respir Cell Mol Biol. 2022 Dec;67(6):695-707. doi: 10.1165/rcmb.2022-0202OC.
Cigarette smoke (CS) is considered a major risk factor for chronic obstructive pulmonary disease (COPD) that is currently the third leading cause of death in the United States. Studies have indicated that patients with COPD have elevated blood low-density lipoprotein levels, which may contribute to the dysregulation of lipid metabolism. Accumulating data show that microRNAs (miRNAs) are involved in various human diseases. However, the role of microRNAs in the pathogenesis of COPD remains poorly defined. In this study, we found that miR-103a expression was significantly reduced in alveolar macrophages from smokers and patients with COPD versus that in alveolar macrophages from nonsmokers. Our data indicated that reactive oxygen species negatively regulate miR-103a in macrophages. Functionally, miR-103a modulates the expressions of genes involved in lipid metabolism and directly targets low-density lipoprotein receptors in macrophages. Furthermore, overexpression of miR-103a suppressed the accumulation of lipid droplets and reduced the reactive oxygen species, both and . Taken together, our findings indicate that downregulation of miR-103a contributes to cigarette smoke-induced lipid-laden macrophage formation and plays a critical role in lipid homeostasis in lung macrophages in the pathogenesis of COPD.
香烟烟雾（CS）被认为是慢性阻塞性肺疾病（COPD）的主要危险因素，目前在美国是第三大致死原因。研究表明，COPD 患者的血液低密度脂蛋白水平升高，这可能导致脂质代谢失调。越来越多的证据表明，microRNAs（miRNAs）参与了各种人类疾病。然而，miRNAs 在 COPD 发病机制中的作用仍未明确。在这项研究中，我们发现吸烟者和 COPD 患者肺泡巨噬细胞中的 miR-103a 表达明显低于非吸烟者肺泡巨噬细胞中的 miR-103a 表达。我们的数据表明，活性氧（ROS）在巨噬细胞中负调控 miR-103a。功能上，miR-103a 调节参与脂质代谢的基因的表达，并直接靶向巨噬细胞中的低密度脂蛋白受体。此外，miR-103a 的过表达抑制了脂质滴的积累，并减少了活性氧，同时减少了炎症反应。综上所述，我们的研究结果表明，miR-103a 的下调导致香烟烟雾诱导的富含脂质的巨噬细胞形成，并在 COPD 发病机制中对肺巨噬细胞中的脂质稳态发挥关键作用。
