miR-128-3p regulates the formation of THP-1-derived foam cells by inhibiting the NOD1/RIP2 signaling pathway
The purpose of this study is to investigate the influence of miR-128-3p on the formation of THP-1-derived foam cells.To this end,THP-1 cells were induced to differentiate into macrophages by phorbol 12-myristate 13-acetate(PMA)and divided into control group,oxidized low-density lipoprotein(ox-LDL)group,miR-NC group,miR-128-3p mimic group,and miR-128-3p mimic+nucleotide-binding oligomerization domain-containing protein 1(NOD1)agonist(iE-DAP)group.Foam cell formation was induced by ox-LDL(100 μg/mL)after the corresponding transfection treatment.The expressions of miR-128-3p,NOD1 mRNA,and lipid accumulation in cells were examined and the content of cholesterol in cells and the levels of TNF-α and IL-6 in cell culture supernatants were detected.Protein expressions of NOD1,receptor-interacting protein 2(RIP2),phosphorylated RIP2(p-RIP2),NF-κB p65(p65),and phosphorylated p65(p-p65)in cells were measured.The targeting between miR-128-3p and NOD1 was validated.The results showed that compared to those of the control group,miR-128-3p level in the ox-LDL group was decreased(P＜0.05),while the lipid content,cholesterol content,NOD1 mRNA and protein levels,p-RIP2/RIP2 and p-p65/p65 ratios,and the TNF-α and IL-6 levels in the cells were all increased(P＜0.05).Compared to those of the ox-LDL group,the expression of miR-128-3p in the miR-128-3p mimic group was increased(P＜0.05),while the expression of NOD1,the phosphorylation of RIP2 and p65,the accumulation of lipid and cholesterol,and the levels of TNF-α and IL-6 were all decreased(P＜0.05).Compared to those of the miR-128-3p mimic group,the expression of NOD1,the phosphorylation of RIP2 and p65,the accumulation of lipid and cholesterol,and the levels of TNF-α and IL-6 were all increased in the miR-128-3p mimic+iE-DAP group(P＜0.05).Compared to cells transfected with miR-NC,cells transfected with miR-128-3p mimic showed decreased activity of luciferase reporter gene containing NOD1-WT(P＜0.05).This study suggests that overexpression of miR-128-3p may inhibit the formation of THP-1-derived foam cells by inhibiting the NOD1/RIP2 signaling pathway.
atherosclerosisfoam cellmacrophagemicroRNA-128-3pnucleotide-binding oligomerization domain-containing protein 1receptor-interacting protein 2
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