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Foxo6在高糖高脂应激诱导血管内皮细胞胰岛素抵抗中的表达及与NF-κB通路的相互作用 被引量:6

Role of Foxo6 in insulin resistance of vascular endothelial cells induced by high glucose and high fat and its interaction with NF-κB pathway
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摘要 目的研究叉头框蛋白(Foxos)在高糖高脂(HG/HF)应激诱导人脐静脉内皮细胞(HUVECs)胰岛素抵抗(IR)中的表达改变及意义。方法首先用HG/HF应激建立内皮细胞IR模型,观察Foxos基因在正常(control)组和HG/HF组中的差异性表达,筛选出Foxos改变最为显著的亚型如Foxo6。通过沉默Foxo6,观察其在内皮细胞IR中的作用;Foxo6介导IR的作用机制是否与NF-κB信号相互作用有关。结果Foxo6在HG/HF应激诱导IR组中变化最显著,并且表达量明显升高,通过小RNA干扰和质粒转染技术,发现靶向Foxo6的siRNA3片段沉默效果最显著,进一步研究发现,沉默Foxo6基因后可明显逆转HG/HF诱导的IR,而且其逆转IR的作用机制与NF-κB信号相互作用有关。结论Foxo6介导了HG/HF应激所致的血管内皮细胞IR,其机制是Foxo6可与NF-κBp65产生相互作用,激活NF-κB通路有关;而沉默Foxo6可改善HG/HF应激所致的血管内皮细胞IR。 Aim To investigate the expression of Foxos in human umbilical vein endothelial cells(HUVECs)with insulin resistance(IR)induced by high glucose and high fat(HG/HF)stress and its significance.Methods First,the IR model of endothelial cells was established by HG/HF stress.The differential expression of Foxos gene in normal(Ctrl)group and HG/HF group was observed,and the subtypes with the most significant changes in Foxos were screened out,such as Foxo6.Next,Foxo6 was silenced to observe its role in endothelial cell with IR.Finally,whether the mechanism of Foxo6-mediated IR was related to the interaction of NF-κB signaling was investigated.Results The expression increase of Foxo6 was the most significant among Foxos under the IR condition induced by HG/HF.Using a small RNA interference and plasmid transfection technique,we found that the silence effect of the siRNA3 fragments targeting Foxo6 was the most significant among the siRNAs.Moreover,the further study showed that silencing the Foxo6 gene could significantly reverse the endothelial IR induced by HG/HF,and the mechanism of the reversal effect was related to the interaction between the Foxo6 and NF-κB signal.Conclusions Foxo6 mediates the endothelial cell IR induced by the HG/HF stress.The underlying mechanism is that Foxo6 can interact with NF-κBp65 and activate NF-κB signaling pathway.Silencing Foxo6 can improve the IR of vascular endothelial cells induced by HG/HF stress.
作者 夏敏 涂以思 熊小伟 牛艾琳 尹婷婷 张雅楠 黄起壬 XIA Min;TU Yi-si;XIONG Xiao-wei;NIU Ai-lin;YIN Ting-ting;ZHANG Ya-nan;HUANG Qi-ren(Key Provincial Laboratory of Basic Pharmacology,Nanchang 330006,China;Dept of Pharmacology,School of Pharmacy,Nanchang University,Nanchang 330006,China;The Third Clinical Medical College, Nanchang University, Nanchang 330006, China)
出处 《中国药理学通报》 CAS CSCD 北大核心 2022年第4期552-561,共10页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No 81960153)。
关键词 叉头框蛋白 高血糖 高血脂 内皮细胞 胰岛素抵抗 核转录因子 forkhead box protein hyperglycemia hyperlipidemia endothelial cells insulin resistance NF-κBp65
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