Proliferation of vascular smooth muscle cells under inflammation is regulated by NF-κB p65/microRNA-17/RB pathway activation

Inflammation and excessive proliferation of vascular smooth muscle cells (VSMCs) have key roles in various vascular disorders, including restenosis, atherosclerosis and pulmonary artery hypertension. However, the underlying mechanism remains unclear. The present study investigated the role of nuclear factor-κB (NF-κB) and microRNA (miRNA) in the regulation of VSMC proliferation under inflammatory conditions. It was demonstrated that miR-17 stimulated the proliferation of VSMCs, enhanced cell cycle G1/S transition, and increased levels of proliferating cell nuclear antigen and E2F1. By directly targeting the retinoblastoma (RB) protein mRNA-3′ untranslated region, miR-17 suppressed the expression of RB. Activation of NF-κB p65 resulted in increased miR-17 expression in VSMCs, whereas inactivation of NF-κB p65 resulted in decreased expression of miR-17 in VSMCs. NF-κB p65 signalling directly regulates miR-17 promoter activity. NF-κB p65 activation also suppressed RB expression, which was abrogated by miR-17 inhibitor. Taken together, the present results indicated that VSMC proliferation is regulated by activation of the NF-κB p65/miR-17/RB pathway. As NF-κB p65 signalling is activated in and is a master regulator of the inflammatory response, the present findings may provide a mechanism for the excessive proliferation of VSMCs under inflammation during vascular disorders and may identify novel targets for the treatment of vascular diseases.