title: microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2.
abstract: Transformation of macrophages into foam cells plays a critical role in the pathogenesis of atherosclerosis. The aim of this study was to determine the expression and biological roles of microRNA (miR)-150 in the formation of macrophage foam cells and to identify its functional target(s). Exposure to 50 μg/ml oxidized low-density lipoprotein (oxLDL) led to a significant upregulation of miR-150 in THP-1 macrophages. Overexpression of miR-150 inhibited oxLDL-induced lipid accumulation in THP-1 macrophages, while knockdown of miR-150 enhanced lipid accumulation. apoA-I- and HDL-mediated cholesterol efflux was increased by 66% and 43%, respectively, in miR-150-overexpressing macrophages relative to control cells. In contrast, downregulation of miR-150 significantly reduced cholesterol efflux from oxLDL-laden macrophages. Bioinformatic analysis and luciferase reporter assay revealed adiponectin receptor 2 (AdipoR2) as a direct target of miR-150. Small interfering RNA-mediated downregulation of AdipoR2 phenocopied the effects of miR-150 overexpression, reducing lipid accumulation and facilitating cholesterol efflux in oxLDL-treated THP-1 macrophages. Knockdown of AdipoR2 induced the expression of proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), ABCA1, and ABCG1. Moreover, pharmacological inhibition of PPARγ or LXRα impaired AdipoR2 silencing-induced upregulation of ABCA1 and ABCG1. Taken together, our results indicate that miR-150 can attenuate oxLDL-induced lipid accumulation in macrophages via promotion of cholesterol efflux. The suppressive effects of miR-150 on macrophage foam cell formation are mediated through targeting of AdipoR2. Delivery of miR-150 may represent a potential approach to prevent macrophage foam cell formation in atherosclerosis.
authors.affiliation: Department of Geratory, Linzi District People's Hospital of Zibo City, Zibo, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of HealthCare, Qilu Hospital of Shandong University (Qingdao), Qingdao City, Qingdao, China. Electronic address: drsuhuangzhang@qq.com.
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002784:Cholesterol; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D054419:Receptors, Adiponectin; C475420:ADIPOR2 protein, human; C533097:MIR150, human; C099252:oxidized low density lipoprotein
keywords: Atherosclerosis; Cholesterol efflux; Foam cell formation; Therapeutic target