应用晚期糖基化终产物受体的特异性核酸适配体阻断细胞NF-κB 信号通路的研究
首发时间:2020-04-08
摘要:晚期糖基化终产物受体(RAGE)激活后参与多种慢性炎症进程,其作用主要通过特异性激活NF-κB信号通路实现。作为炎症反应主要信号通路之一,NF-κB过度激活是参与了各种免疫类疾病如类风湿性关节炎、肿瘤和移植排斥反应等进程。因此,开发阻断NF-κB信号通路的药物有助于炎症的治疗。为探究RAGE的特异核酸适配体是否可用于靶向炎症的药物开发,本文构建并筛选过表达RAGE的人胚肾HEK293T细胞和结直肠癌细胞系HCT116细胞。基于受体RAGE与配体蛋白S100B结合激活NF-κB信号通路的模型,本文探究RAGE的核酸适配体阻断NF-κB信号的作用。结果表明,受体RAGE的核酸适配体特异性结合细胞的RAGE,并有效抑制了受体RAGE的激活以及下游的NF-κB信号转导。本研究为进一步开发靶向炎症反应的RAGE阻断的核酸适配体药物提供理论依据。
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The Aptamer of the Receptor of Advanced Glycation End Products (RAGE) Efficiently Blocks NF-κB signaling
Abstract:The activation of the receptor of advanced glycation end products (RAGE) is associated with a variety of chronic inflammation. NF-κB signaling is the primary mediator of RAGE activation. As one of the central cytokines and signaling pathways for inflammatory responses, excessive activation of NF-κB has been demonstrated in the pathogenesis of various immunological diseases such as rheumatoid arthritis, tumors, and transplant rejection. Therefore, the development of an inhibitor of NF-κB signaling may improve the therapeutics of inflammation. In order to investigate the role of aptamer as a targeted drug for the treatment of inflammation, we utilized the RAGE highly expressed HCT-116 cells and established RAGE-overexpressed 293T cell line.Using an S100B as the ligand of RAGE, we established an NF-κB activation model to explore the inhibitory effect of RAGE aptamer. The results indicate that the RAGE aptamer specifically binds RAGE, blocks the activation of RAGE, and efficiently inhibits the activation of NF-κB signaling. This study provides preliminary evidence to develop the aptamer-based drug targeting the RAGE-mediated inflammation.
Keywords: Biochemistry and molecular biology RAGE NF-κB Aptamer
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应用晚期糖基化终产物受体的特异性核酸适配体阻断细胞NF-κB 信号通路的研究
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