MicroRNA-126 Priming Enhances Functions of Endothelial Progenitor Cells under Physiological and Hypoxic Conditions and Their Therapeutic Efficacy in Cerebral Ischemic Damage.

MicroRNA-126 Priming Enhances Functions of Endothelial Progenitor Cells under Physiological and Hypoxic Conditions and Their Therapeutic Efficacy in Cerebral Ischemic Damage.
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MicroRNA-126启动增强生理和缺氧条件下内皮祖细胞的功能及其对脑缺血损伤的治疗作用

DOI:
10.1155/2018/2912347
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发表时间:
2018
影响因子:
4.3
通讯作者:
Ma X
Ma X
中科院分区:
医学3区
文献类型:
--
作者:
Pan Q;Zheng J;Du D;Liao X;Ma C;Yang Y;Chen Y;Zhong W;Ma X

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内皮祖细胞(EPCs)已显示出治疗缺血性卒中(IS)的潜力,而据报道microRNA-126(miR-126)对内皮功能和血管生成具有有益作用。在本研究中,我们研究了miR-126过表达对EPCs的影响,并探讨了miR-126-primed EPCs(EPCmiR-126)治疗IS的疗效。测定miR-126过表达对EPC增殖、迁移、管形成能力、活性氧(ROS)产生和一氧化氮(NO)产生的影响。在体内研究中,测定EPCmiR-126对脑血流量(CBF)、神经功能缺损评分(NDS)、梗死体积、脑微血管密度(cMVD)和血管生成的影响。此外,测量循环EPCs(cEPCs)及其所含miR-126的水平。我们发现(1)miR-126过表达促进EPCs的增殖、迁移和管腔形成能力,通过激活PI 3 K/Akt/eNOS通路减少ROS,增加NO的产生;(2)EPCmiR-126比EPCs更有效地减少梗死体积和NDS,增加cMVD、CBF和血管生成;(3)EPCmiR-126的灌注增加了cEPCs中miR-126的数量和水平。我们的数据表明,miR-126过表达增强EPCs在体外和体内的功能。
Endothelial progenitor cells (EPCs) have shown the potential for treating ischemic stroke (IS), while microRNA-126 (miR-126) is reported to have beneficial effects on endothelial function and angiogenesis. In this study, we investigated the effects of miR-126 overexpression on EPCs and explore the efficacy of miR-126-primed EPCs (EPCmiR-126) in treating IS. The effects of miR-126 overexpression on EPC proliferation, migratory, tube formation capacity, reactive oxygen species (ROS) production, and nitric oxide (NO) generation were determined. In in vivo study, the effects of EPCmiR-126 on the cerebral blood flow (CBF), neurological deficit score (NDS), infarct volume, cerebral microvascular density (cMVD), and angiogenesis were determined. Moreover, the levels of circulating EPCs (cEPCs) and their contained miR-126 were measured. We found (1) miR-126 overexpression promoted the proliferation, migration, and tube formation abilities of EPCs; decreased ROS; and increased NO production of EPCs via activation of PI3K/Akt/eNOS pathway; (2) EPCmiR-126 was more effective than EPCs in attenuating infarct volume and NDS and enhancing cMVD, CBF, and angiogenesis; and (3) infusion of EPCmiR-126 increased the number and the level of miR-126 in cEPCs. Our data indicate that miR-126 overexpression enhanced the function of EPCs in vitro and in vivo.
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发表时间: 2012
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