MicroRNA-21 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting activator protein-1.

Objectives: This study is to investigate whether microRNA (miR)-21 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell (VSMC) proliferation and migration through targeting activator protein-1 (AP-1). Methods: VSMCs were transfected with the miR-21 or miR-21 inhibitor. Cell proliferation was determined using methyl thiazolyl tetrazolium assay. Cell migration was detected by transwell assay. Luciferase reporter assay was used to study the interaction between miR-21 and AP-1. The levels of mRNA were determined using quantitative real-time polymerase chain reaction, while protein expression was measured using Western blotting assay. Results: Low expression of miR-21 significantly inhibited VSMC proliferation, invasion and migration. The mRNA levels and protein expression of alpha-SMA and AP-1 were down-regulated by low expression of miR-21. In addition, luciferase reporter assay demonstrated that AP-1 might be a direct target gene of miR-21 in VSMC initiation and development. Moreover, up-regulation of AP-1 was critical for miR-21-mediated inhibitory effects on platelet-derived growth factor-induced cell proliferation and migration in human VSMCs. Conclusions: In summary, miR-21 is a key molecule in regulating human VSMC proliferation and migration by targeting AP-1, suggesting that specific modulation of miR-21 in human VSMCs may become an attractive approach for the treatment of proliferative vascular diseases.