MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4
MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4
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DOI：
10.1002/jcp.26389
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发表时间：
2018-10-01
影响因子：
5.6
通讯作者：
Ke, Zun-Ping
中科院分区：
文献类型：
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作者：
Qin, Song-Bai;Peng, Da-Yan;Ke, Zun-Ping
MicroRNAs （miRNAs）在多种生物过程中发挥着多种作用，miR-182-5p的异常表达与多种疾病有关。然而，miR-182-5p在动脉粥样硬化（AS）中的作用仍然知之甚少。本研究采用氧化低密度脂蛋白（ox-LDL）在RAW264.7细胞中建立AS模型。miR-182-5p在AS模型中呈剂量依赖性和时间依赖性显著降低。此外，miR-182-5p模拟物可抑制CD36、油红染色水平、TC和TG，同时通过增强SOD活性抑制ROS水平、MDA和细胞凋亡。同样，将miR-182-5p抑制剂转染RAW264.7细胞时，显示出相反的结果。众所周知，toll样受体4 （TLR4）与许多炎症疾病有关。通过生物信息学分析，TLR4被认为是miR-182-5p的潜在靶点。我们观察到TLR4在AS模型中被激活，miR-182-5p可以通过体外靶向TLR4抑制AS的进展。综上所述，我们发现miR-182-5p通过灭活TLR4表达抑制氧化应激和细胞凋亡，在AS中发挥重要作用。
MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR-182-5p has been involved in many diseases. However, the role miR-182-5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low-density lipoprotein (ox-LDL) in RAW264.7 cells. miR-182-5p was markedly decreased in AS model dose-dependently and time-dependently. Additionally, CD36, oil-red staining levels, TC, and TG were inhibited by miR-182-5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR-182-5p inhibitors were transfected into RAW264.7 cells. It is well known that toll-like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR-182-5p. We observed TLR4 was activated in AS models and miR-182-5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR-182-5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression.