Protective effect of KLF15 on vascular endothelial dysfunction induced by TNF‑α.
Protective effect of KLF15 on vascular endothelial dysfunction induced by TNF‑α.
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DOI：
10.3892/mmr.2018.9195
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发表时间：
2018-08
影响因子：
3.4
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Liu B;Xu L;Yu X;Li W;Sun X;Xiao S;Guo M;Wang H
动脉粥样硬化（atheropathy，AS）是一种发病率较高的心血管疾病。Krüppel样因子15（KLF 15）在许多病理过程中发挥作用，包括肾病、糖代谢异常和心肌损伤。本研究旨在探讨KLF 15在血管内皮功能障碍中的作用。采用MTT比色法、一氧化氮（NO）检测法和细胞粘附检测试剂盒分别检测肿瘤坏死因子（TNF）-α对Eahy 926细胞的存活率、粘附力和NO释放量的影响。采用逆转录-定量聚合酶链反应（RT-PCR）和免疫印迹法（Western blot）检测KLF 15、内皮型一氧化氮合酶（eNOS）、单核细胞趋化蛋白1（MCP-1）、细胞间粘附分子1（ICAM-1）、转化生长因子β1（TGF-β1）、磷酸化（p-）转录因子p65（p65）和核因子红细胞2相关因子2（Nrf 2）。本研究结果表明，TNF-α在10 ng/ml的最佳浓度下能够诱导Eahy 926细胞的血管内皮功能障碍。过表达KLF 15可显著提高TNF-α诱导的Eahy 926细胞的存活率和NO释放量，并增加eNOS和Nrf 2的表达水平。TNF-α诱导Eahy 926细胞凋亡后，KLF 15的过表达可明显抑制细胞粘附率，并下调MCP-1、ICAM-1、TGF-β1和p-p65的表达。结论：KLF 15过表达对TNF-α诱导的Eahy 926细胞功能障碍具有保护作用，其机制可能与激活Nrf 2信号通路和抑制核因子κB信号通路有关。
Atherosclerosis (AS) is a cardiovascular disease with a relatively high incidence rate. Krüppel-like factor 15 (KLF15) has a role in numerous pathological processes, including nephropathy, abnormal glucose metabolism and myocardial injury. The aim of the present study was to investigate the function of KLF15 in vascular endothelial dysfunction. MTT analyses, nitric oxide (NO) detection and cell adhesion detection kits were used to investigate the viability and adhesion of, and quantity of NO released by Eahy926 cells induced by tumor necrosis factor (TNF)-α, respectively. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to determine the expression levels of KLF15, endothelial nitric oxide synthase, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-β1 (TGF-β1), phosphorylated (p-)transcription factor p65 (p65) and nuclear factor erythroid 2-related factor 2 (Nrf2). The results of the present study demonstrated that TNF-α was able to induce vascular endothelial dysfunction in Eahy926 cells at an optimum concentration of 10 ng/ml. Overexpression of KLF15 markedly enhanced cell viability in addition to the quantity of released NO of TNF-α-induced Eahy926 cells, and increased the expression levels of eNOS and Nrf2. Furthermore, overexpression of KLF15 markedly suppressed the rate of cellular adhesion, and downregulated levels of MCP-1, ICAM-1, TGF-β1 and p-p65 in TNF-α induced Eahy926 cells. In conclusion, the results of the present study suggested that overexpression of KLF15 in Eahy926 cells exhibited a protective effect against TNF-α induced dysfunction via activation of Nrf2 signaling and inhibition of nuclear factor κB signaling.
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影响因子：
64.5
作者：
Moore KJ;Tabas I
通讯作者：
Tabas I
DOI：
10.1161/atvbaha.112.300349
发表时间：
2012-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Fan Y;Guo Y;Zhang J;Subramaniam M;Song CZ;Urrutia R;Chen YE
通讯作者：
Chen YE
影响因子：
3.7
作者：
Moon S;Oh CM;Choi MK;Park YK;Chun S;Choi M;Yu JM;Yoo HJ
通讯作者：
Yoo HJ
影响因子：
--
作者：
Crofford, LJ;Tan, B;Hla, T
通讯作者：
Hla, T
影响因子：
7.2
作者：
Karelis, A;Brochu, M;Rabasa-Lhoret, R
通讯作者：
Rabasa-Lhoret, R