Attenuated macrophage activation mediated by microRNA‑183 knockdown through targeting NR4A2

Gong,Fu-Han; Long,Li; Yang,Yong-Sheng; Shen,De-Hong; Zhang,Yu-Song; Wang,Xue-Sheng; Zhang,Xue-Ping; Xiao,Xiao-Qiang

doi:10.3892/etm.2021.9731

Attenuated macrophage activation mediated by microRNA‑183 knockdown through targeting NR4A2

Authors:
- Fu-Han Gong
- Li Long
- Yong-Sheng Yang
- De-Hong Shen
- Yu-Song Zhang
- Xue-Sheng Wang
- Xue-Ping Zhang
- Xiao-Qiang Xiao
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Affiliations: Department of Cardiology, Tongren Municipal People's Hospital, Tongren, Guizhou 554300, P.R. China, Department of Clinical Laboratory, Tongren Municipal People's Hospital, Tongren, Guizhou 554300, P.R. China
Published online on: January 29, 2021 https://doi.org/10.3892/etm.2021.9731
Article Number: 300

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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.

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