Department of Endocrinology, The Affiliated Hospital of Medical School, Ningbo Universtiy, Ningbo, China.
Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6922-6929. doi: 10.26355/eurrev_201810_16162.
To explore the specific role of TUG1 in regulating the occurrence and progression of diabetic atherosclerosis and its underlying mechanism.
TUG1 expressions in coronary artery disease (CAD) tissues, normal arterial tissues, endothelial cells induced by high-dose glucose and tumor necrosis factor-α (TNF-α) were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The effects of TUG1 on proliferation, migration and cell cycle of human umbilical vein endothelial cells (HUVECs) were detected by cell counting kit-8 (CCK-8), transwell assay and flow cytometry, respectively. Subsequently, protein expressions of proliferation-related genes, cell cycle-related genes and Wnt pathway-related genes were detected by Western blot after altering TUG1 expression in HUVECs. Further rescue experiments were carried out to explore whether TUG1 could regulate diabetic atherosclerosis via Wnt pathway.
Overexpressed TUG1 was found in CAD tissues and endothelial cells induced by high-dose glucose and TNF-α compared with those of controls. TUG1 overexpression remarkably promoted proliferation, migration and cell cycle of HUVECs. Protein expressions of β-catenin and c-Myc were upregulated by overexpression of TUG1. Rescue experiments indicated that XAV-939, the inhibitor of Wnt pathway, could partially reverse the increased proliferative and migratory changes in HUVECs induced by TUG1 overexpression.
We found that overexpressed TUG1 stimulates proliferation and migration of endothelial cells via Wnt pathway, thereby promoting the occurrence and progression of diabetic atherosclerosis.
探讨 TUG1 在调控糖尿病动脉粥样硬化发生发展中的具体作用及其机制。
采用实时定量聚合酶链反应（qRT-PCR）检测冠心病（CAD）组织、正常动脉组织、高浓度葡萄糖和肿瘤坏死因子-α（TNF-α）诱导的内皮细胞中 TUG1 的表达。采用细胞计数试剂盒-8（CCK-8）、Transwell 检测和流式细胞术分别检测 TUG1 对人脐静脉内皮细胞（HUVEC）增殖、迁移和细胞周期的影响。然后，通过改变 HUVEC 中 TUG1 的表达，检测增殖相关基因、细胞周期相关基因和 Wnt 通路相关基因的蛋白表达。进一步进行挽救实验，探讨 TUG1 是否通过 Wnt 通路调节糖尿病动脉粥样硬化。
与对照组相比，CAD 组织和高浓度葡萄糖及 TNF-α诱导的内皮细胞中 TUG1 的表达上调。TUG1 过表达显著促进 HUVEC 的增殖、迁移和细胞周期。TUG1 的过表达上调了β-连环蛋白和 c-Myc 的蛋白表达。挽救实验表明，Wnt 通路抑制剂 XAV-939 可部分逆转 TUG1 过表达诱导的 HUVEC 增殖和迁移变化。
我们发现，过表达的 TUG1 通过 Wnt 通路刺激内皮细胞的增殖和迁移，从而促进糖尿病动脉粥样硬化的发生和发展。
