TIM-3 inhibits PDGF-BB-induced atherogenic responses in human artery vascular smooth muscle cells

Abstract

Increasing evidence suggests that T-cell immunoglobulin and mucin domain 3 (TIM-3) displays anti-atherosclerotic effects, but its role in vascular smooth muscle cells (VSMCs) has not been reported. The present study aimed to investigate the function of TIM-3 and its roles in human artery VSMCs (HASMCs). A protein array was used to investigate the TIM-3 protein expression profile, which indicated that TIM-3 expression was increased in the serum of patients with lower extremity arteriosclerosis obliterans disease (LEAOD) compared with healthy individuals. Immunohistochemistry and western blotting of arterial tissue further revealed that TIM-3 expression was increased in LEAOD artery tissue compared with normal artery tissue. Additionally, platelet-derived growth factor-BB (PDGF-BB) displayed a positive correlation with TIM-3 expression in HASMCs. TIM-3 decreased the migration and proliferation of PDGF-BB-induced HASMCs, and anti-TIM-3 blocked the effects of TIM-3. The effect of TIM-3 on the proliferation and migration of HASMCs was further investigated using LV-TIM-3-transduced cells. The results revealed that TIM-3 also inhibited PDGF-BB-induced expression of the inflammatory factors interleukin-6 and tumor necrosis factor-α by suppressing NF-κB activation. In summary, the present study revealed that TIM-3 displayed a regulatory role during the PDGF-BB-induced inflammatory reaction in HASMCs, which indicated that TIM-3 may display anti-atherosclerotic effects.