miRNAs through β-ARR2/p-ERK1/2 pathway regulate the VSMC proliferation and migration.

Abstract Background miRNAs are involved in plaque formation of atherosclerosis and vessel restenosis. In this study, we investigated the effects of miR-599, miR-204, and miR-181b on VSMC proliferation, and migration through TGFβ receptor 2 (TGFβR2), β-arrestin 2 (β-ARR2), SMAD2/p-SMAD2, and ERK1/2/p-ERK1/2. Materials & methods Genes and miRNAs were predicted by bioinformatics tools and were transfected by PEI-miRNAs (miR-599, miR-204, and miR-181b) complexes into VSMCs. The gene and protein expression levels were evaluated by real-time RT-PCR and western blotting techniques, respectively. The VSMC proliferation and migration were studied by MTT and scratch assay, respectively. Results The miR-181b and miR-204 downregulated significantly β-ARR2 gene and protein expression levels and p-ERK1/2 values. Moreover, TGFβR2 gene and protein expression levels and p-SMAD2 values were not significantly affected by miR-181b and miR-204. The VSMC proliferation (p = 0.0019, p = 0.0054, respectively) and migration (p  Conclusion The results suggested that the inhibitory effects of miR-181b and miR-204 on VSMC proliferation and migration are mediated by the β-ARR2/p-ERK1/2 pathway. Since VSMC proliferation and migration are involved in plaque growth, therefore this pathway can be a therapeutic target for atherosclerosis.