miR-144、miR-21-3p、miR-142-5p 及 miR-27b-3p 对心肌梗塞后血管再生的作用
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1.广东省实验动物重点实验室/ 广东省实验动物监测所,广州 510663; 2. 广东省农业动物基因组学与分子 育种重点实验室/ 华南农业大学,广州 510642

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Effects of miR-144, miR-21-3p, miR-142-5p and miR-27b-3p on angiogenesis after myocardial infarction
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1.Guangdong Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China. 2. Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642

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    摘要:

    目的 以五指山小型猪心肌梗塞模型为研究对象,筛选对心肌梗塞易感且可能调控血管生成素-2 (ANGPT-2 ,促血管生长和形成的重要基因)表达的 miRNAs。 以人脐静脉内皮细胞(HUVECs)为细胞模型,探索候 选 miRNAs 对人脐静脉内皮细胞的增殖、迁移及细胞血管形成中的作用。 方法 通过小 RNA 测序和生物信息学软 件预测靶标于 ANGPT-2 ,并且在心肌梗塞组和对照组中差异表达的 miRNAs,利用 Edu 法、Transwell 法、体外实验法 检测候选 miRNAs 对 HUVECs 的增殖、迁移和血管成腔的影响。 结 果 miR-144、 miR-21-3p、 miR-142-5p 及 miR-27b-3p是潜在的靶标于 ANGPT-2 ,并且在心肌梗塞和对照两组表达水平差异显著的 miRNAs。 miR-144 不能直接影响 HUVECs 的增殖,但能抑制细胞的迁移及血管形成;miR-21-3p 能抑制 HUVECs 增殖和迁移,但促进 HUVECs 血管形成;miR-142-5p 和 miR-27b-3p 能抑制 HUVECs 增殖、迁移及管;miR-142-5p 和 miR-27b-3p 能显著抑制ANGPT-2 的转录表达。 结论 心肌梗塞后,miR-142-5p 和 miR-27b-3p 可能通过靶标于 ANGPT-2 的 3′UTR 并且抑制ANGPT-2 的转录表达,抑制血管内皮细胞的增殖、迁移及血管形成,进而抑制血管再生。

    Abstract:

    Objective To explore the effects of microRNAs ( miRNAs ) on proliferation, migration and angiogenesis in a miniature pig model of myocardial infarction (MI). The miRNAs differently expressed between MI and control pigs were selected, in particular those potentially targeting the ANGPT-2 gene ( an important growth factor during angiogenesis), and their effects on proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) were investigated. Methods Bioinformatics software was used to predict the differentially expressed miRNAs targeting ANGPT-2 in the MI and control groups. The effects of miRNAs on the proliferation, migration and angiogenesis of HUVECS were detected by EdU staining proliferation, transwell chamber and in vitro experimental method, respectively. Results miR-144, miR-21-3p, miR-142-5p and miR-27b-3p were found to potentially target ANGPT-2 and were significantly differently expressed between the MI and control groups. In HUVECs, miR-144 had no significant effect on proliferation, but significantly inhibited migration and vessel formation; miR-21-3p inhibited proliferation and migration, but promoted vessel formation; miR-142-5p and miR-27b-3p inhibited proliferation, migration and vessel formation. Of these four miRNAs, miR-142-5p and miR-27b-3p significantly inhibited the expression of ANGPT-2 mRNA. Conclusions After MI, miR-142-5p and miR-27b-3p may inhibit angiogenesis by suppressing the proliferation, migration and vessel formation of vascular endothelial cells, by targeting the 3′ UTR of ANGPT-2 and down-regulating ANGPT-2 mRNA expression.

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袁晓龙,潘金春,蒋瑶,龚宝勇,高洪彬,白国锋,谭伟江,梁十,李加琪,张豪,王希龙. miR-144、miR-21-3p、miR-142-5p 及 miR-27b-3p 对心肌梗塞后血管再生的作用[J].中国实验动物学报,2020,28(3):297~306.

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  • 收稿日期:2019-11-01
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  • 在线发布日期: 2020-07-03
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