KLF7 通过激活冠心病患者心外膜脂肪组织中的 NF-κB 信号通路促进巨噬细胞活化。
KLF7 promotes macrophage activation by activating the NF-κB signaling pathway in epicardial adipose tissue in patients with coronary artery disease.
机构信息
Medicine Department, Shihezi University, Shihezi, Xinjiang, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):7002-7014. doi: 10.26355/eurrev_202006_21693.
OBJECTIVE
Inflammatory accumulation in epicardial adipose tissue (EAT) may influence the formation and development of coronary artery disease (CAD). EAT macrophages exhibit M1 polarization and the secretion of a large number of inflammatory factors in CAD patients. Emerging data demonstrate that Krüppel-like factor-7 (KLF7), contributes to the regulation of adipocyte differentiation and the secretion of adipose tissue inflammation. However, the function of KLF7 in EAT inflammation still remains to be uncovered. This study aims to investigate the role of KLF7 in macrophage activation in EAT.
PATIENTS AND METHODS
The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels were measured by Real Time-PCR. The protein expression level was detected by Western blot.
RESULTS
The expression of inflammatory factors and KLF7 were markedly increased in CAD EAT than non-CAD EAT. KLF7 is highly expressed in human THP-1-derived macrophages induced by inflammatory stimuli, such as LPS. The knockdown of KLF7 inhibited the release of inflammatory factors and significantly decreased the expression of KLF7 in human THP-1-derived macrophages stimulated by LPS. Moreover, transfection with KLF7-siRNA caused the marked inhibition of LPS-induced phosphorylation of JNK-MAPKs and also suppressed the levels of p-p65 and inhibited the activation of p-IκBα.
CONCLUSIONS
Taken together, these results indicate that KLF7 enhances macrophage activation, mediated by JNK-NF-κB signaling pathways in EAT. This suggests that KLF7 may be a potential therapeutic target for cardiovascular diseases such as CAD.
目的
心包脂肪组织（EAT）中的炎症积聚可能影响冠状动脉疾病（CAD）的形成和发展。CAD 患者的 EAT 巨噬细胞表现出 M1 极化和大量炎症因子的分泌。新出现的数据表明，Krüppel 样因子 7（KLF7）有助于调节脂肪细胞分化和脂肪组织炎症的分泌。然而，KLF7 在 EAT 炎症中的功能仍有待揭示。本研究旨在探讨 KLF7 在 EAT 中巨噬细胞激活中的作用。
患者和方法
通过酶联免疫吸附试验（ELISA）测量细胞上清液中白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平。通过实时 PCR 测量 mRNA 表达水平。通过 Western blot 检测蛋白表达水平。
结果
CAD EAT 中的炎症因子和 KLF7 的表达明显高于非 CAD EAT。KLF7 在由炎症刺激（如 LPS）诱导的人 THP-1 衍生的巨噬细胞中高度表达。KLF7 的敲低抑制了炎症因子的释放，并显著降低了 LPS 刺激的人 THP-1 衍生巨噬细胞中 KLF7 的表达。此外，KLF7-siRNA 的转染导致 LPS 诱导的 JNK-MAPKs 磷酸化明显抑制，并抑制 p-p65 的水平，抑制 p-IκBα 的激活。
结论
综上所述，这些结果表明，KLF7 通过 JNK-NF-κB 信号通路增强了 EAT 中的巨噬细胞激活。这表明 KLF7 可能是 CAD 等心血管疾病的潜在治疗靶点。
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