Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2
Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2
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DOI：
10.3389/fcimb.2019.00366
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发表时间：
2019-10-29
影响因子：
5.7
通讯作者：
Wang, Tong-jian
中科院分区：
文献类型：
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作者：
Li, Na;Liu, Shi-feng;Wang, Tong-jian
背景资料：越来越多的证据表明幽门螺杆菌与冠心病（coronary heart disease，CHD）相关，但其潜在机制尚不清楚。使用蛋白质印迹法检测蛋白质水平，并使用电子显微镜评估外泌体。利用荧光素酶报告系统鉴定miR-25的靶基因。pylori感染增加了胃上皮细胞中miR-25的表达，并与人外周血中外泌体传递的miR-25水平增加相关。机制研究表明Kruppel样因子2（KLF 2）是血管内皮细胞中外泌体传递的miR-25的直接靶点。此外，miR-25/KLF 2轴还可调节NF-κ B信号通路，导致白细胞介素6（IL 6）、单核细胞趋化蛋白-1（MCP-1）、血管细胞粘附分子-1（VCAM-1）和细胞间粘附分子-1（ICAM-1）表达增加。幽门相关性冠心病此外，外周血中高水平的外泌体传递的miR-25可能对CHD构成潜在风险。
Background: Increasing evidence has shown that Helicobacter pylori is associated with coronary heart disease (CHD); however, the underlying mechanism remains unclear.Methods: The expression of miR-25 and mRNAs was measured using qRT-PCR. Protein levels were detected using western blotting and exosomes were assessed with an electron microscope. The target gene of miR-25 was identified using the luciferase report system.Results: H. pylori infection increased the expression of miR-25 in gastric epithelial cells and was associated with increased levels of exosome-transmitted miR-25 in human peripheral blood. Mechanistic investigation showed the Kruppel-like factor 2 (KLF2) was a direct target of exosome-transmitted miR-25 in vascular endothelial cells. In addition, the miR-25/KLF2 axis regulated the NF-kappa B signaling pathway, resulting in increased expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1).Conclusion: Our findings suggest that the miR-25/KLF2 axis may be a potential therapeutic target for H. pylori-associated CHD. Furthermore, high levels of exosome-transmitted miR-25 in peripheral blood may pose a potential risk for CHD.