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Updated: Nov 13, 2025
Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages
Published on: November 3, 2014
Attenuated macrophage activation mediated by microRNA-183 knockdown through targeting NR4A2
Fu-Han Gong1, Li Long2, Yong-Sheng Yang1
1Department of Cardiology, Tongren Municipal People's Hospital, Tongren, Guizhou 554300, P.R. China.
Abstract:
Atherosclerosis is considered a chronic inflammatory disease, and macrophages function as important mediators in the development of atherogenesis. MicroRNA (miR)-183 is a small non-coding RNA that acts as a novel tumor suppressor and has recently been proposed to affect cardiac hypertrophy. However, the exact role and underlying mechanism of miR-183 in macrophage activation remain unknown. In the present study, miR-183 showed upregulated expression in atheromatous plaques and in bone marrow-derived macrophages (BMDMs) subjected to stimulation with oxidized low-density lipoproteins. Using a miR-183 loss-of-function strategy, it was demonstrated that miR-183 knockdown significantly increased resolving M2 macrophage marker expression but decreased proinflammatory M1 macrophage marker expression, as well as attenuated NF-κB activation. Moreover, decreased foam-cell formation accompanied by upregulation of genes involved in cholesterol efflux and downregulation of genes implicated in cholesterol influx was found in BMDMs transfected with a miR-183 inhibitor. Mechanistically, macrophage activation mediated by miR-183 silencing was partially attributed to direct upregulation of NR4A2 expression in BMDMs. Thus, the present study suggests that neutralizing miR-183 may be a potential therapeutic strategy for the treatment of atherosclerosis.
Insights
MicroRNA-183 (miR-183) promotes atherosclerosis by activating macrophages. Neutralizing miR-183 reduces inflammation and foam cell formation, suggesting it as a potential therapeutic target for atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Atherosclerosis is a chronic inflammatory disease driven by macrophage activity.
- MicroRNA-183 (miR-183) is implicated in cardiac hypertrophy, but its role in macrophage activation and atherosclerosis is unclear.
Purpose of the Study:
- To investigate the role and mechanism of miR-183 in macrophage activation during atherogenesis.
- To determine if miR-183 modulation affects macrophage polarization and foam cell formation.
Main Methods:
- Examined miR-183 expression in atherosclerotic plaques and oxidized LDL-stimulated bone marrow-derived macrophages (BMDMs).
- Utilized a loss-of-function strategy (miR-183 inhibitor) in BMDMs.
- Assessed macrophage polarization markers (M1/M2), NF-κB activation, foam cell formation, and cholesterol metabolism genes.
- Investigated the role of NR4A2 in miR-183-mediated macrophage activation.
Main Results:
- miR-183 expression was upregulated in atherosclerotic plaques and activated BMDMs.
- miR-183 knockdown enhanced M2 macrophage markers, reduced M1 markers, and attenuated NF-κB activation.
- Inhibition of miR-183 decreased foam cell formation, increased cholesterol efflux genes, and decreased cholesterol influx genes.
- miR-183 silencing led to NR4A2 upregulation, partially mediating the observed effects.
Conclusions:
- miR-183 plays a pro-atherogenic role by promoting M1 macrophage polarization and foam cell formation.
- Neutralizing miR-183 ameliorates key features of atherosclerosis in macrophages.
- Targeting miR-183 represents a potential therapeutic strategy for atherosclerosis treatment.
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