Dysregulation of miR-103a Mediates Cigarette Smoking–induced Lipid-laden Macrophage Formation

MicroRNA Control Lipid-laden Alveolar Macrophages in Smokers: A Potential Therapeutic Target for Chronic Obstructive Pulmonary Disease?

“…They focused their study on miR-103a, a miRNA strongly expressed in myeloid cells and involved in non–small-cell lung cancer (NSCLC) and bronchiolitis obliterans syndrome ( 19 , 20 ). Zhu and colleagues also report that the miR103a expression is strongly decreased in AMs from both smokers and patients with COPD, an effect directly linked to the consequences of CS exposure as showed by in vitro experiments ( 18 ). However, the defect in miR-103a is similar between smokers and patients with COPD, and it remains to be determined if this is a marker of CS exposure or if it contributes to COPD physiopathology.…”

“…In this issue of the Journal , Zhu and colleagues (pp. 695–707 ) report on studies of miRNA in COPD pathogenesis and specifically in the control of AM, one of the first cells exposed to CS ( 18 ). They focused their study on miR-103a, a miRNA strongly expressed in myeloid cells and involved in non–small-cell lung cancer (NSCLC) and bronchiolitis obliterans syndrome ( 19 , 20 ).…”

“…In addition, Zhu and colleagues demonstrated that the modulation of miR-103a by CS is related to both cytoplasmic and mitochondrial oxidative stress, a result supported by the inhibitory effect of an antioxidant (N-acetylcysteine) ( 18 ). In addition, exposure of macrophages to an oxidative stress (H 2 0 2 ) also inhibits miR-103a expression, whereas modulation of mitochondrial stress did not affect the miR-103a expression.…”

“…Functionally, miR-103a directly controls lipid metabolism in macrophages and specifically low-density lipoprotein receptor (LDLR) mRNA and membrane expression ( 18 ). Indeed, in vitro and in vivo experiments confirmed that miR-103a controls lipid accumulation in macrophages and the expression of LDLR.…”

“…Both proinflammatory cytokines and proteases play a key role in the physiopathology of COPD by amplifying inflammatory cell recruitment and airway remodeling. Interestingly, miR-103a also has the ability to modulate mRNA expression of metalloproteases such as ADAM10 ( 19 , 23 ) and interleukins ( IL-1β and TNFα ) ( 18 ). However, the role of miR-103a during the response to CS in murine experimental models needs further study, as does the relationship between the inflammatory status, the disease severity, and the expression of this miRNA in patients with COPD.…”