Metformin inhibits angiogenesis of endothelial progenitor cells via miR-221-mediated p27 expression and autophagy
Metformin inhibits angiogenesis of endothelial progenitor cells via miR-221-mediated p27 expression and autophagy
复制标题
二甲双胍通过 miR-221 介导的 p27 表达和自噬抑制内皮祖细胞的血管生成
DOI：
10.4155/fmc-2019-0017
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发表时间：
2019-09-01
影响因子：
4.2
通讯作者：
Li, Xiao-Qiang
中科院分区：
文献类型：
--
作者：
Ni, Hai-Zhen;Liu, Zhao;Li, Xiao-Qiang
目的：探讨二甲双胍对内皮祖细胞（EPCs）血管生成能力的影响及其机制。结果如下：EPC生长和miR-221表达随二甲双胍的浓度依赖性降低，并且在miR-221表达和二甲双胍浓度之间观察到负相关性（p < 0.001）。使用模拟物的miR-221过表达降低了EPCs中二甲双胍介导的血管生成作用（p < 0.01）。二甲双胍增加p27和LC 3 II表达和AMP活化蛋白激酶（AMPK）磷酸化，降低p62表达，而miR-221过表达逆转二甲双胍的作用。此外，化合物C对AMPK的抑制逆转了p27和LC 3 II水平的增加以及AMPK磷酸化或miR-221 siRNA处理。结论：美托洛尔抑制EPCs的血管生成能力。其潜在机制涉及AMPK介导的自噬途径活性并增加miR-221介导的p27表达。
Aim: To explore the underlying mechanisms of metformin on the angiogenic capacity of endothelial progenitor cells (EPCs). Results: EPC growth and miR-221 expression decreased concentration-dependence with metformin, and a negative correlation was observed between miR-221 expression and metformin concentration (p < 0.001). miR-221 overexpression using a mimic decreased the metformin-mediated angiogenic effects in EPCs (p < 0.01). Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin. Additionally, AMPK inhibition by compound C reversed the increase in p27 and LC3II levels and AMPK phosphorylation or miR-221 siRNA treatment. Conclusion: Metformin inhibits the angiogenic capacity of EPCs. The underlying mechanism involves AMPK-mediated autophagy pathway activity and increases miR-221-mediated p27 expression.