miR-193a-5p Inhibits Macrophage Lipid Accumulation via the HDAC9-ABCA1/G1 Pathway
10.13865/j.cnki.cjbmb.2024.10.1244
- VernacularTitle:miR-193a-5p通过HDAC9-ABCA1/G1途径抑制巨噬细胞脂质蓄积
- Author:
Yan WANG
1
;
Zhi-Yong SONG
1
;
Wei-Min AI
1
;
Jin-Xing CAI
1
Author Information
1. 湘潭医卫职业技术学院,医学基础课部,湖南 湘潭411102
- Publication Type:Journal Article
- Keywords:
miR-193a-5p;
histone deacetylase 9(HDAC9);
ATP-binding cassette transporter A1/G1 (ABCA1/G1);
lipid accumulation;
macrophage
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(12):1751-1760
- CountryChina
- Language:Chinese
-
Abstract:
Previous studies have shown that microRNA-193a-5p (miR-193a-5p) was related to fatty acid metabolism in epithelial cells,whereas its role in macrophage lipid accumulation is unclear.Histone deacetylase 9 (HDAC9) could deacetylate ATP-binding cassette transporter A1/G1 (ABCA1/G1) and decrease their expression,inhibiting macrophage cholesterol efflux and promoting foam cell formation.This study explores the effects of miR-193a-5p on lipid accumulation in THP-1 macrophages and its rela-tionship with HDAC9.RT-PCR showed that miR-193a-5p levels were significantly decreased in THP-1-derived foam cells.RT-PCR and Western blotting results suggested that miR-193a-5p overexpression sig-nificantly up-regulated the mRNA and protein levels of ABCA1 and ABCG1,while it did not affect the expression of SR-A,SR-BI or CD36.Oil Red O staining and liquid scintillation counting indicated that miR-193a-5p mimic transfection markedly promoted cholesterol efflux and decreased lipid droplet num-bers without altering the uptake of DiL-ox-LDL.High-performance liquid chromatography (HPLC) assay showed that miR-193a-5p overexpression decreased intracellular contents of total cholesterol (TC),cho-lesterol ester (CE),and free cholesterol (FC) in THP-1-derived foam cells.These inhibitory effects of miR-193a-5p on foam cell formation became more evident after HDAC9 siRNA treatment and were mainly reversed by HDAC9 overexpression (P<0.05) .Furthermore,luciferase reporter assay and Western blot-ting showed that miR-193a-5p directly targeted HDAC93'UTR,thereby down-regulating its protein ex-pression (P<0.05) .Altogether,miR-193a-5p inhibits lipid accumulation in THP-1 macrophages via the HDAC9-ABCA1/G1 pathway.
