MiR-126 promotes endothelial cell apoptosis by targeting PI3K/Akt in rats with lower limb arteriosclerosis obliterans

被引:15
作者
Li, W. -M. [1 ]
Yue, J. -N. [1 ]
Guo, D. -Q. [1 ]
Fu, W. -G. [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Vasc Surg, Shanghai, Peoples R China
关键词
MiR-126; P-Akt; Lower limb arteriosclerosis obliterans; PROGENITOR CELLS; UP-REGULATION; ANTISENSE; MICRORNA; PATHWAY; ARTERY; LOX-1;
D O I
10.26355/eurrev_201908_18664
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
OBJECTIVE: To investigate the influence of micro ribonucleic acid (miR)-126 on the rats with lower limb arteriosclerosis obliterans (ASO). MATERIALS AND METHODS: Male Sprague-Dawley rats aged 3 months old were randomly divided into Sham operation group (Control group, n=10) and Model group (n=10), and the model of lower limb ASO was established. After modeling, the expression of miR-126 in arteries was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the change in the downstream signaling pathway was examined via Western blotting. The human umbilical vein endothelial cells (HU-VECs) were induced by oxidized low-density lipoprotein (Ox-LDL) to establish the model of endothelial injury, followed by detection of miR-126 expression. Then, the Luciferase assay was performed to verify the downstream target gene of miR-126. After being cultured, HUVECs were set as Control group, Ox-LDL induction group, and Ox-LDL + miR-126 inhibitor group, and the expressions of phosphorylated-protein kinase B (p-Akt) and cleaved cysteine-aspartic protease -3 (Caspase-3) were detected in the above groups. RESULTS: After the establishment of the model, the expression level of miR-126 was raised in vessels, but the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt signals were weakened (p<0.01). Ox-LDL-induced endothelial cell apoptosis promoted the expression of miR-126, and the difference was statistically significant. The bioinformatics analysis results showed that PI3KR2 was a direct target of miR-126, which was also proven via the Luciferase assay. Moreover, the transfection with miR-126 inhibitor into endothelial cells suppressed Ox-LDL-induced cell apoptosis, thereby persistently activating the PI3K/Akt signaling pathway (p<0.01). CONCLUSIONS: In rats with lower limb arteriosclerosis obliterans (ASO), miR-126 represses the PI3K/Akt signaling pathway to accelerate endothelial cell apoptosis.
引用
收藏
页码:327 / 333
页数:7
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