MicroRNA1 modulates oxLDL-induced hyperlipidemia by down-regulating MLCK and ERK/p38 MAPK pathway
MicroRNA1 modulates oxLDL-induced hyperlipidemia by down-regulating MLCK and ERK/p38 MAPK pathway
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MicroRNA1通过下调MLCK和ERK/p38 MAPK通路调节oxLDL诱导的高脂血症
DOI：
10.1016/j.lfs.2014.04.028
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发表时间：
2014-06-27
期刊：
影响因子：
6.1
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
--
作者：
Zhu, Hua-Qing;Wang, Feng;Wang, Yuan
目标：本研究旨在探讨microRNA 1（miR 1）在oxLDL介导的人脐静脉内皮细胞（HUVECs）肌球蛋白轻链激酶（MLCK）激活中的作用。通过miRNA平板测定试剂盒和mirVana（TM）miRNA分离试剂盒测定MiR 1表达。分别采用Western blot、实时荧光定量PCR和γ-P-32-ATP磷酸掺入法检测MLCK蛋白、转录本和激酶活性。Western blot检测MLC、ERK和p38的磷酸化水平。结果显示，oxLDL处理后，miR 1表达降低，而MLCK表达增加，并呈时间和剂量依赖性。与此一致，miR 1模拟物阻止MLCK表达和激活，并减弱oxLDL处理的HUVEC中MLC和ERK/p38的磷酸化。此外，我们发现，miR 1能够结合位于MLCK mRNA的3 '非翻译区的一个位点，并抑制其express.Significance：两者合计，这项研究表明，miR 1对高脂血症的影响是通过下调MLCK和ERK/p38 MAPK通路介导的。(C)2014爱思唯尔公司All rights reserved.
Aims: This study was aimed to determine whether microRNA1 (miR1) plays a role in the activation of myosin light chain kinase (MLCK) mediated by oxLDL in human umbilical vein endothelial cells (HUVECs).Main methods: HUVECs were treated with oxLDL along with a control miR or miR1 mimic. MiR1 expression was assayed by miRNA plate assay kit and mirVana (TM) miRNA isolation kit. The MLCK protein, transcript, and kinase activity were measured by Western blot, real-time-polymerase chain reaction and gamma-P-32-ATP phosphate incorporation, respectively. In addition, phosphorylation of MLC, ERK and p38 was analyzed by Western blot.Key findings: The results showed that upon treatment with oxLDL, miR1 expression was decreased, whereas MLCK expression was increased, in a time- and dose-dependent manner. Consistent with this, miR1 mimic prevented MLCK expression and activation and attenuated the phosphorylation of MLC and ERK/p38 in oxLDL-treated HUVECs. Furthermore, we showed that miR1 was able to bind a site located at the 3'un-translational region of MLCK mRNA and inhibited its expression.Significance: Taken together, this study demonstrated that the effect of miR1 on hyperlipidemia is mediated through down-regulation of MLCK and the ERK/p38 MAPK pathway. (C) 2014 Elsevier Inc. All rights reserved.