Department of Neurology, the First Hospital of Yulin, Yulin, Shaanxi, China.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12867-12877. doi: 10.26355/eurrev_202012_24190.
To determine the effect of miR-217 on the apoptosis of atherosclerotic endothelial cells (AECs) through the Toll-like receptor (TLR) 4/PI3K/Akt/NF-κB pathway.
Oxidized low-density lipoprotein (ox-LDL) was used to construct an atherosclerotic endothelial cell model, and the expression of miR-217/TLR4/PI3K/Akt/NF-κB in the cells was regulated to explore their effects on the viability, apoptosis, inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)], and endothelial-to-mesenchymal transformation (EndMT) of the endothelial cells.
In AECs, miR-217 expression decreased, and the PI3K/Akt/NF-κB pathway was inhibited. The Dual-Luciferase reporter assay revealed that TLR4 was the target of miR-217, and it was up-regulated in AECs, and the further study revealed that up-regulation of miR-217 protected AECs, increased their activity, reduced their apoptosis, and inhibited inflammatory response and EndMT, while TLR4 acted contrary to miR-217. Besides, it was also found that miR-217 inhibited the PI3K/Akt/NF-κB pathway, thus weakening the influence of si-TLR4 on endothelial cells. Furthermore, miR-217 inhibited EndMT by inhibiting TLR4 from activating the PI3K/Akt/NF-κB signal pathway.
In AECs, TLR4 expression increased, and miR-217 and the PI3K/Akt/NF-κB signaling pathway are inhibited. Additionally, miR-217 can increase the viability of AECs through the TLR4/PI3K/Akt/ NF-κB signal transduction pathway, and inhibit their apoptosis, inflammatory response, and EndMT.
通过 Toll 样受体（TLR）4/PI3K/Akt/NF-κB 通路，研究 miR-217 对动脉粥样硬化内皮细胞（AEC）凋亡的影响。
采用氧化低密度脂蛋白（ox-LDL）构建动脉粥样硬化内皮细胞模型，调控细胞中 miR-217/TLR4/PI3K/Akt/NF-κB 的表达，探讨其对内皮细胞活力、凋亡、炎症因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）]及内皮-间充质转化（EndMT）的影响。
在 AEC 中，miR-217 表达下调，PI3K/Akt/NF-κB 通路被抑制。双荧光素酶报告基因检测显示 TLR4 是 miR-217 的靶基因，在 AEC 中上调，进一步研究表明上调 miR-217 可保护 AEC，增加其活性，减少其凋亡，并抑制炎症反应和 EndMT，而 TLR4 则与 miR-217 作用相反。此外，还发现 miR-217 抑制 PI3K/Akt/NF-κB 通路，从而削弱了 si-TLR4 对内皮细胞的影响。进一步研究发现，miR-217 通过抑制 TLR4 激活 PI3K/Akt/NF-κB 信号通路，抑制 EndMT。
在 AEC 中，TLR4 表达增加，miR-217 及 PI3K/Akt/NF-κB 信号通路受到抑制。此外，miR-217 可通过 TLR4/PI3K/Akt/NF-κB 信号转导通路增加 AEC 的活力，抑制其凋亡、炎症反应和 EndMT。
