MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity.
MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity.
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DOI：
10.1016/j.bbrc.2010.02.045
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发表时间：
2010-03-19
影响因子：
3.1
通讯作者：
Searles, Charles D.
中科院分区：
文献类型：
--
作者：
Weber, Martina;Baker, Meredith B.;Moore, Jeffrey P.;Searles, Charles D.
与血流相关的机械力在调节内皮细胞（EC）中的血管信号和基因表达中起重要作用。microRNA（miRNAs）是一类转录后调节基因表达的非编码RNA，参与细胞的分化、生长、增殖和凋亡等多种功能。已知miRNA在调节EC生物学中具有重要作用，但其在经受剪切应力条件的细胞中的表达和功能是未知的。我们试图确定在人类内皮细胞受到单向剪切应力的miRNA表达谱，并确定miR-21在剪切应力诱导的EC功能变化中的作用。对暴露于长时间单向剪切应力（USS，24小时，15达因/cm 2）的HUVEC进行的TLDA阵列和qRT-PCR分析鉴定了13种表达显著上调的miRNA（p < 0.05）。变化最大的miRNA是miR-21;与对照细胞相比，USS处理的细胞中miR-21增加了5.2倍（p = 0.002）。Western分析表明，PTEN，miR-21的已知靶点，在暴露于USS或用pre-miR-21转染的HUVECs中下调。重要的是，过表达miR-21的HUVEC细胞凋亡减少，eNOS磷酸化和一氧化氮（NO）产生增加。这些数据表明，剪切力调节内皮细胞中的miRNA的表达，并且miR-21通过减少细胞凋亡和激活NO通路来影响内皮生物学。这些研究推进了我们对切应力调节血管稳态的机制的理解。
Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24 hrs, 15 dynes/cm2) identified 13 miRNAs whose expression was significantly upregulated (p < 0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p = 0.002) in USStreated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis.
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影响因子：
5.3
作者：
Wang Y;Lee CG
通讯作者：
Lee CG
DOI：
10.1152/ajpheart.00233.2008
发表时间：
2008-12-01
影响因子：
4.8
作者：
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影响因子：
4.8
作者：
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通讯作者：
Kontos, CD
DOI：
10.1115/1.3138276
发表时间：
1981-01-01
影响因子：
1.7
作者：
DEWEY, CF;BUSSOLARI, SR;DAVIES, PF
通讯作者：
DAVIES, PF
影响因子：
20.1
作者：
Kuehbacher, Angelika;Urbich, Carmen;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie