Division of Vascular Surgery, Guangdong Key Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Laboratory of General Surgery, Guangdong Key Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Mol Med Rep. 2020 Aug;22(2):886-894. doi: 10.3892/mmr.2020.11167. Epub 2020 May 21.
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.
越来越多的证据表明 T 细胞免疫球蛋白和粘蛋白结构域 3（TIM-3）具有抗动脉粥样硬化作用，但它在血管平滑肌细胞（VSMCs）中的作用尚未报道。本研究旨在探讨 TIM-3 的功能及其在人动脉平滑肌细胞（HASMCs）中的作用。通过蛋白质芯片研究 TIM-3 蛋白表达谱，结果表明下肢动脉硬化闭塞症（LEAOD）患者血清中 TIM-3 表达增加，与健康个体相比。动脉组织的免疫组化和蛋白质印迹分析进一步表明，LEAOD 动脉组织中 TIM-3 的表达高于正常动脉组织。此外，血小板衍生生长因子-BB（PDGF-BB）与 HASMCs 中的 TIM-3 表达呈正相关。TIM-3 减少了 PDGF-BB 诱导的 HASMCs 的迁移和增殖，而抗 TIM-3 阻断了 TIM-3 的作用。通过转导 LV-TIM-3 的细胞进一步研究了 TIM-3 对 HASMCs 增殖和迁移的影响。结果表明，TIM-3 通过抑制 NF-κB 激活，还抑制了 PDGF-BB 诱导的炎症因子白细胞介素-6 和肿瘤坏死因子-α的表达。总之，本研究揭示了 TIM-3 在 HASMCs 中 PDGF-BB 诱导的炎症反应中具有调节作用，表明 TIM-3 可能具有抗动脉粥样硬化作用。
