Advanced Glycation End Products Induce Proliferation and Migration of Human Aortic Smooth Muscle Cells through PI3K/AKT Pathway

Abstract

Advanced glycation end products (AGEs) have been widely regarded as an important inducing factor in the pathogenesis of diabetic arteriosclerosis, and the proliferation and migration of vascular smooth muscle cells (VSMCs) are also involved in this process. However, it is not clear whether AGEs promote atherosclerosis by inducing the proliferation and migration of VSMCs. To figure out this question, this study investigated the effects of AGEs on the proliferation and migration of human aorta vascular smooth muscle cells (HASMCs) and the underlying mechanisms. This study evaluated the effects of different concentrations of AGEs on cell proliferation and migration. CCK8, transwell, and western blotting assays demonstrated that AGEs significantly increased cell proliferation and migration in a concentration-dependent manner and that the optimal proproliferative and promigratory concentrations of AGEs were 10 mg/L and 20 mg/L, respectively. AGE-induced cell proliferation, migration, and expression of filament actin (F-actin) were markedly attenuated by a PI3K inhibitor (LY2940002). Additionally, the phosphorylation of AKT was reduced when the receptor of advanced glycation end product (RAGE) gene was silenced by lentivirus transfection, which led to a concomitant reduction of the expression of proliferation and migration-related proteins. These data indicate that AGEs may activate the PI3K/AKT pathway through RAGE and thus facilitate the proliferation and migration of HASMCs.