Effects of miR-34b-5p on atherosclerosis-associated foam cell formation and inflammatory response by targeting IGFBP1 expression
10.3969/j.issn.1000-484X.2025.04.018
- VernacularTitle:miR-34b-5p通过靶向调控IGFBP1表达对动脉粥样硬化泡沫细胞形成及炎症反应的影响
- Author:
Hui HUI
1
;
Guangpeng WU
;
Mei LIAO
;
Guangzhi LI
Author Information
1. 海南省中医院心血管内科,海口 570203
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
miR-34b-5p;
IGFBP1;
Foam cells;
Inflammatory
- From:
Chinese Journal of Immunology
2025;41(4):879-884
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of miR-34b-5p in formation of atherosclerosis(AS)-associated foam cells and in-flammation,and its possible mechanism.Methods:Expression levels of miR-34b-5p and insulin-like growth factor binding protein-1(IGFBP1)mRNA in serum of 34 AS patients and 20 healthy controls were detected.RAW264.7 macrophages were treated with oxi-dized low-density lipoprotein(ox-LDL)to construct AS foam cell model,and expression levels of miR-34b-5p and IGFBP1 mRNA in foam cells were detected.Interaction between miR-34b-5p and IGFBP1 was verified by dual luciferase reporter gene assay.miR-34b-5p inhibitor(inhibitor),inhibitor negative control(inhibitor-NC),IGFBP1 siRNA plasmid(si-IGFBP1)and siRNA negative control(si-NC)were separately or co-transfected into RAW264.7 macrophages.Lipid deposition ability of foam cells was observed,and levels of intracellular total cholesterol(TC),IL-1β,IL-6 and TNF-α were detected.Results:Compared with healthy controls,miR-34b-5p was highly expressed in serum of AS patients(P<0.05),while expression of IGFBP1 mRNA was lower(P<0.05).ox-LDL treatment significantly increased expression of miR-34b-5p(P<0.05),while significantly reduced expression of IGFBP1 mRNA in RAW264.7 macrophages(P<0.05).Dual luciferase reporter assay showed that IGFBP1 was the target gene of miR-34b-5p.Compared with inhibi-tor-NC group,expression of IGFBP1 protein in RAW264.7 macrophages in inhibitor group was increased significantly(P<0.05).After ox-LDL induction,miR-34b-5p inhibitor inhibited lipid deposition ability of macrophages,and decreased levels of intracellular TC,IL-1β,IL-6 and TNF-α.Interfering expression of IGFBP1 gene could reverse the intervention effect of miR-34b-5p inhibitor on macro-phages by enhance lipid deposition ability of macrophages,and increase levels of intracellular TC,IL-1β,IL-6 and TNF-α.Conclu-sion:Down-regulation of miR-34b-5p expression can inhibit the formation of AS-associated foam cells and inflammatory response,and the mechanism may be realized by targeting up-regulation of IGFBP1 expression.
