miR-21 regulates vascular smooth muscle cell function in arteriosclerosis obliterans of lower extremities through AKT and ERK1/2 pathways.

introductionArteriosclerosis obliterans (ASO) is a disease that affects the lower extremities. The mechanism of ASO is associated with the proliferation and migration of vascular smooth muscle cells (VSMCs). miR-21 plays a key role in various biological processes of the cardiovascular system, associated with the proliferation, migration and apoptosis of VSMCs. It is unclear, however, if miR-21 is involved in the regulation of ASO. MATERIAL AND

methodsHuman aortic smooth muscle cells (HASMCs) were transfected with miR-21 mimics and co-treated with protein kinase B (AKT) or a mitogen-activated protein kinase (ERK) inhibitor. Expression levels of p-AKT or p-ERK were measured by western blot. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and visualized under a fluorescence microscope. Cell proliferation was monitored by bromodeoxyuridine (BrdU) labeling; cell migration and invasion were determined by the Transwell assay.

resultsmiR-21 was upregulated in arteries of ASO, the pathogenesis of which involved the activation of p-AKT and p-ERK1/2. Inhibition of the AKT or ERK activity was consistent with the attenuation of the miR-21-induced HASMC migration and proliferation. HASMCs co-treated with miR-21 mimics and AKT or ERK inhibitor showed attenuation of the miR-21-induced high elongation ratio.

conclusionsWe demonstrated that the expression of miR-21 in HASMCs could find potential application in cardiac therapy. Inhibition of the activity of AKT or ERK could attenuate miR-21-induced cell proliferation and migration as well as altering morphology of HASMCs. The present study aimed to indicate the potential roles of miR-21 in ASO processes, and the results provided a novel therapeutic approach for treating ASO and new targets for preventing ASO in earlier stages.