Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries.
Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries.
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let-7a 和 let-7b 对氧化低密度脂蛋白诱导的内皮细胞损伤的保护作用。
DOI：
10.1371/journal.pone.0106540
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhou HH
中科院分区：
文献类型：
--
作者：
Bao MH;Zhang YW;Lou XY;Cheng Y;Zhou HH
凝集素样低密度脂蛋白受体1（LOX-1）是内皮细胞中氧化低密度脂蛋白（oxLDL）的受体。氧化低密度脂蛋白激活脂氧合酶-1（LOX-1）可促进内皮细胞凋亡和功能障碍，参与动脉粥样硬化的形成。然而，LOX-1的调节因素仍不清楚。MicroRNA是一类内源性的非编码小RNA，在转录后水平调控基因表达。let-7家族是第二个被发现的microRNA家族，在心血管疾病中起重要作用。Let-7a和let-7 b以LOX-1 3′-UTR为靶点，在内皮细胞中高表达。本研究表明LOX-1是let-7a和let-7 b的靶点。它们通过靶向LOX-1 3′-UTR的310-316位点抑制LOX-1的表达。过表达let-7a和let-7 b可抑制oxLDL诱导的内皮细胞凋亡、NO缺乏、ROS过度产生、LOX-1上调和内皮型一氧化氮合酶（eNOS）下调。此外，oxLDL处理还可诱导p38 MAPK磷酸化、NF-κB核转位、IκB降解和PKB去磷酸化。Let-7a或let-7 b过表达显著减弱了这些改变。本研究可能为let-7a和let-7 b预防心血管疾病（如动脉粥样硬化）相关的内皮功能障碍提供新的见解。
Lectin-like low-density lipoprotein receptor 1 (LOX-1) is a receptor for oxidized low density lipoprotein (oxLDL) in endothelial cells. The activation of LOX-1 by oxLDL stimulates the apoptosis and dysfunction of endothelial cells, and contributes to atherogenesis. However, the regulatory factors for LOX-1 are still unclear. MicroRNAs are small, endogenous, non-coding RNAs that regulate gene expressions at a post-transcriptional level. The let-7 family is the second microRNA been discovered, which plays important roles in cardiovascular diseases. Let-7a and let-7b were predicted to target LOX-1 3′-UTR and be highly expressed in endothelial cells. The present study demonstrated that LOX-1 was a target of let-7a and let-7b. They inhibited the expression of LOX-1 by targeting the positions of 310-316 in LOX-1 3′-UTR. Over-expression of let-7a and let-7b inhibited the oxLDL-induced endothelial cell apoptosis, NO deficiency, ROS over-production, LOX-1 upregulation and endothelial nitric oxide synthase (eNOS) downregulation. Moreover, we found that oxLDL treatment induced p38MAPK phosphorylation, NF-κB nuclear translocation, IκB degradation and PKB dephosphorylation. Let-7a or let-7b over-expression attenuated these alterations significantly. The present study may provide a new insight into the protective properties of let-7a and let-7b in preventing the endothelial dysfunction associated with cardiovascular disease, such as atherosclerosis.
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影响因子：
20.1
作者：
Mehta, Jawahar L.;Sanada, Nobuhito;Sawamura, Tatsuya
通讯作者：
Sawamura, Tatsuya
影响因子：
20.1
作者：
Kuehbacher, Angelika;Urbich, Carmen;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
64.8
作者：
Reinhart, BJ;Slack, FJ;Ruvkun, G
通讯作者：
Ruvkun, G
影响因子：
15.9
作者：
Knowles, JW;Reddick, RL;Maeda, N
通讯作者：
Maeda, N
影响因子：
3.3
作者：
Ou, Hsiu-Chung;Song, Tuzz-Ying;Lee, Shin-Da
通讯作者：
Lee, Shin-Da