Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Mol Med Rep. 2018 Aug;18(2):1987-1994. doi: 10.3892/mmr.2018.9195. Epub 2018 Jun 20.
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.
动脉粥样硬化（AS）是一种发病率相对较高的心血管疾病。Krüppel 样因子 15（KLF15）在许多病理过程中发挥作用，包括肾病、异常葡萄糖代谢和心肌损伤。本研究旨在探讨 KLF15 在血管内皮功能障碍中的作用。使用 MTT 分析、一氧化氮（NO）检测试剂盒和细胞黏附检测试剂盒分别检测肿瘤坏死因子（TNF）-α诱导的 Eahy926 细胞活力和黏附、NO 释放量。采用逆转录-定量聚合酶链反应和 Western blot 分析检测 KLF15、内皮型一氧化氮合酶、单核细胞趋化蛋白-1（MCP-1）、细胞间黏附分子-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（Nrf2）的表达水平。本研究结果表明，TNF-α在 10ng/ml 的最佳浓度下能够诱导 Eahy926 细胞发生血管内皮功能障碍。KLF15 的过表达除了增强 TNF-α诱导的 Eahy926 细胞中 NO 的释放量外，还显著增强了细胞活力，并增加了 eNOS 和 Nrf2 的表达水平。此外，KLF15 的过表达还显著抑制了细胞黏附率，并下调了 TNF-α诱导的 Eahy926 细胞中 MCP-1、ICAM-1、TGF-β1 和 p-p65 的水平。综上所述，本研究结果表明，在 Eahy926 细胞中过表达 KLF15 通过激活 Nrf2 信号通路和抑制核因子 κB 信号通路，对 TNF-α诱导的功能障碍表现出保护作用。
