MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways.
MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways.
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DOI：
10.1002/emmm.201202318
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发表时间：
2013-07
影响因子：
11.1
通讯作者：
Fish, Jason E.
中科院分区：
文献类型：
--
作者：
Cheng, Henry S.;Sivachandran, Nirojini;Lau, Andrew;Boudreau, Emilie;Zhao, Jimmy L.;Baltimore, David;Delgado-Olguin, Paul;Cybulsky, Myron I.;Fish, Jason E.
内皮中炎症通路的激活有助于血管疾病，包括败血症和动脉粥样硬化。我们证明，miR-146 a和miR-146 b在内皮细胞暴露于促炎细胞因子后被诱导。尽管miR-146 a/B基因座的快速转录诱导部分由EGR-3介导，但与白细胞粘附分子的表达相比，miR-146 a/B诱导被延迟和持续，并且实际上与炎性基因表达的下调一致。我们证明了miR-146负调控炎症。miR-146 a的过表达减弱了内皮激活，而体外敲低miR-146 a/B或在小鼠中缺失miR-146 a具有相反的效果。miR-146抑制促炎性NF-κB途径以及MAP激酶途径和下游EGR转录因子。最后，我们证明HuR是一种RNA结合蛋白，通过抑制内皮型一氧化氮合酶（eNOS）的表达来促进内皮激活，是一种新的miR-146靶点。因此，我们发现了一个重要的负反馈调节回路，控制可能影响血管炎性疾病的内皮细胞中的促炎信号。
Activation of inflammatory pathways in the endothelium contributes to vascular diseases, including sepsis and atherosclerosis. We demonstrate that miR-146a and miR-146b are induced in endothelial cells upon exposure to pro-inflammatory cytokines. Despite the rapid transcriptional induction of the miR-146a/b loci, which is in part mediated by EGR-3, miR-146a/b induction is delayed and sustained compared to the expression of leukocyte adhesion molecules, and in fact coincides with the down-regulation of inflammatory gene expression. We demonstrate that miR-146 negatively regulates inflammation. Over-expression of miR-146a blunts endothelial activation, while knock-down of miR-146a/b in vitro or deletion of miR-146a in mice has the opposite effect. MiR-146 represses the pro-inflammatory NF-κB pathway as well as the MAP kinase pathway and downstream EGR transcription factors. Finally, we demonstrate that HuR, an RNA binding protein that promotes endothelial activation by suppressing expression of endothelial nitric oxide synthase (eNOS), is a novel miR-146 target. Thus, we uncover an important negative feedback regulatory loop that controls pro-inflammatory signalling in endothelial cells that may impact vascular inflammatory diseases.
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DOI：
10.1111/j.1749-6632.2010.05784.x
发表时间：
2010-01-01
期刊：
INNATE INFLAMMATION AND STROKE
影响因子：
--
作者：
De Caterina, Raffaele;Massaro, Marika;Carluccio, Maria Annunziata
通讯作者：
Carluccio, Maria Annunziata
影响因子：
3.5
作者：
Perry, Mark M.;Williams, Andrew E.;Lindsay, Mark A.
通讯作者：
Lindsay, Mark A.
DOI：
10.1016/j.carpath.2012.06.006
发表时间：
2013-01
期刊：
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
影响因子：
--
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
影响因子：
10.8
作者：
Albrecht, Claudia;Preusch, Michael R.;Bea, Florian
通讯作者：
Bea, Florian
影响因子：
20.1
作者：
Harja, E;Bucciarelli, LG;Yan, SF
通讯作者：
Yan, SF