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微小RNA-130a激活血管内皮生长因子受体2/信号转导与转录激活因子3/缺氧诱导因子1α轴,以增强内皮祖细胞在缺氧状态下的血管再生能力。

miR-130a activates the VEGFR2/STAT3/HIF1α axis to potentiate the vasoregenerative capacity of endothelial colony-forming cells in hypoxia.

作者信息

Guduric-Fuchs Jasenka, Pedrini Edoardo, Lechner Judith, Chambers Sarah E J, O'Neill Christina L, Mendes Lopes de Melo Joana, Pathak Varun, Church Rachel H, McKeown Stuart, Bojdo James, Mcloughlin Kiran J, Stitt Alan W, Medina Reinhold J

机构信息

Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.

出版信息

Mol Ther Nucleic Acids. 2021 Jan 20;23:968-981. doi: 10.1016/j.omtn.2021.01.015. eCollection 2021 Mar 5.

Abstract

Hypoxia modulates reparative angiogenesis, which is a tightly regulated pathophysiological process. MicroRNAs (miRNAs) are important regulators of gene expression in hypoxia and angiogenesis. However, we do not yet have a clear understanding of how hypoxia-induced miRNAs fine-tune vasoreparative processes. Here, we identify miR-130a as a mediator of the hypoxic response in human primary endothelial colony-forming cells (ECFCs), a well-characterized subtype of endothelial progenitors. Under hypoxic conditions of 1% O, miR-130a gain-of-function enhances ECFC pro-angiogenic capacity and potentiates their vasoreparative properties . Mechanistically, miR-130a orchestrates upregulation of VEGFR2, activation of STAT3, and accumulation of HIF1α via translational inhibition of . These findings unveil a new role for miR-130a in hypoxia, whereby it activates the VEGFR2/STAT3/HIF1α axis to enhance the vasoregenerative capacity of ECFCs.

摘要

缺氧可调节修复性血管生成,这是一个受到严格调控的病理生理过程。微小RNA(miRNA)是缺氧和血管生成过程中基因表达的重要调节因子。然而,我们尚未清楚了解缺氧诱导的miRNA如何微调血管修复过程。在此,我们确定miR-130a是人类原代内皮集落形成细胞(ECFC)缺氧反应的介质,ECFC是一种特征明确的内皮祖细胞亚型。在1%氧气的缺氧条件下,miR-130a功能获得增强了ECFC的促血管生成能力并增强了它们的血管修复特性。从机制上讲,miR-130a通过对[未提及的内容]的翻译抑制来协调VEGFR2的上调、STAT3的激活和HIF1α的积累。这些发现揭示了miR-130a在缺氧中的新作用,即它激活VEGFR2/STAT3/HIF1α轴以增强ECFC的血管再生能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4c/7869000/c8d54b4ae22e/fx1.jpg

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