| MiR-197-3p/STAMP2对ox-LDL诱导的人脐静脉内皮细胞凋亡及炎症应激的影响 |
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| 引用本文： | 朱伟军,张卫萍,乌宇亮,王亭忠,杜媛,白晓君.MiR-197-3p/STAMP2对ox-LDL诱导的人脐静脉内皮细胞凋亡及炎症应激的影响[J].心脏杂志,2018,30(6):642-646. |
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| 作者姓名： | 朱伟军 张卫萍 乌宇亮 王亭忠 杜媛 白晓君 |
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| 作者单位： | 西安交通大学第一附属医院心内科, 陕西 西安 710061 |
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| 摘 要： | 目的 探究miR-197-3p/前列腺六次跨膜蛋白（Six transmembrane protein of prostate，STAMP）2对氧化型低密度脂蛋白（ox-LDL）诱导的人脐静脉内皮细胞（HUVECs）凋亡和炎症应答。 方法 用ox-LDL处理HUVEC复制内皮细胞损伤模型；RT-PCR检测miR-197-3p和STAMP2表达；ELISA检测细胞凋亡；Western blot用于检测STAMP2，Bax和Bcl-2的蛋白水平；ELISA检测HUVECs中细胞间黏附分子（ICAM）-1，血管内皮细胞黏附分子（VCAM）-1和E选择素（E-selectin）的表达水平；生物信息学预测miR-197-3p的靶基因；并采用双萤光素酶报告系统、qRT-PCR及Western blot验证miR-197-3p与STAMP2的靶向调控关系。 结果 ox-LDL能明显上调miR-197-3p的表达（P<0.05），同时降低STAMP2的表达（P<0.05），且呈时间依赖性；下调miR-197-3p能够显著抑制ox-LDL诱导的细胞凋亡（P<0.05），同时降低促凋亡蛋白Bax并增加抑凋亡蛋白Bcl-2（P<0.05）；抑制miR-197-3p明显降低ox-LDL诱导的炎症因子的表达（P<0.05）；此外，生物信息学预测提示STAMP2是miR-197-3p的靶基因，而且qRT-PCR及Western blot结果显示抑制miR-197-3p明显上调STAMP2 mRNA和蛋白水平（P<0.05），从而证实miR-197-3p能够靶向调控STAMP2。 结论 MiR-197-3p可以通过靶向调控STAMP2从而调节ox-LDL诱导的HUVECs凋亡及炎症应答，为动脉粥样硬化的靶向治疗提供理论基础。
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| 关 键 词： | miR-197-3p 细胞凋亡 炎症应答 STAMP2 人脐静脉内皮细胞 |
| 收稿时间： | 2017-12-12 |
Effects of miR-197-3p/STAMP2 on human umbilical vein endothelial cell apoptosis and inflammatory response induced by ox-LDL |
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| Affiliation: | Department of Cardiology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China |
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| Abstract: | AIM To investigate the effect of miR-197-3p/STAMP2 on apoptosis and inflammation responses of human umbilical vein endothelial cells (HUVECs) induced by oxidized low density lipoprotein (ox-LDL). METHODS A cell injury model was induced by ox-LDL. RT-PCR was used to detect levels of miR-197-3p and STAMP2 and ELISA analysis were used to determined cell apoptosis. The protein expression of STAMP2, Bax and Bcl-2 were measured by Western blot and expression levels of inter-cellular adhesion molecule (ICAM)-1, vasculareen adhesion molecule (VCAM)-1 and E-selectin were detected by ELISA assay. Bioinformatics analysis identified the potential target of miR-197-3p. The targeting effect of miR-197-3p on STAMP2 was verified by dual-luciferase reporter assay system, Western blot and qRT-PCR. RESULTS ox-LDL induced the level of miR-197-3p and significantly down-regulated the expression of STAMP2 in a time dependent manner in HUVECs (P<0.05). Down-regulating miR-197-3p inhibited ox-LDL-induced cell apoptosis accompanied by a decrease in the expression of Bax and an increase in the expression of Bcl-2 (P<0.05), and attenuated Caspase-3 activity (P<0.05). Moreover, inhibiting the expression of miR-197-3p strongly attenuated the level of inflammatory factors CAM-1, VCAM-1 and E-selectin induced by ox-LDL (P<0.05). The present investigation indicated that STAMP2 was a direct and functional target of miR-197-3p. qRT-PCR and Western blot analysis showed that inhibition of miR-197-3p upregulated the mRNA and protein expression, which validated that miR-197-3p negatively regulated STAMP2. CONCLUSION Our findings indicate that miR-197-3p is involved in cell apoptosis and inflammatory response of HUVECs induced by ox-LDL through targeting STAMP2, which provides a potential target for treatment of atherosclerosis in future. |
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