通过抑制TXNIP介导的氧化应激,降低REDD1 Knockdown可以改善内皮细胞衰老
Qingqiu Chen1, Rong Hu1, Hongmei Qiu1
1Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of Pharmacy, Chongqing Medical University, Chongqing 400010, China.
Mechanisms of ageing and development
|July 14, 2024
概括
在发育和DNA损伤反应1 (REDD1) 中受到调节,通过增加活性氧物种 (ROS) 来促进内皮细胞衰老和动脉样硬化. 抑制REDD1可能为动脉样硬化提供治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 分子医学是分子医学.
背景情况:
- 内皮细胞衰老,以反应性氧物种 (ROS) 和炎症为标志,驱动动动脉硬化 (AS).
- 在发育和DNA损伤反应1 (REDD1) 中受到调节,是一种应激反应蛋白,影响与年龄相关的疾病,但其在内皮细胞衰老中的作用尚不清楚.
研究的目的:
- 研究REDD1在内皮细胞衰老中的作用及其对动脉样硬化的贡献.
- 阐明REDD1调节老化的内皮细胞中ROS产生的机制.
主要方法:
- 生物信息查确定了REDD1作为AS中差异表达的衰老相关基因.
- 在AS和老化小鼠模型中,确定了D-银糖 (DG) 诱导的衰老内皮细胞.
- 分析了REDD1的表达;应用了siRNA和N-乙半氨酸 (NAC) 治疗来评估REDD1的功能和ROS-REDD1反循环,包括TXNIP-REDD1相互作用.
主要成果:
- 在AS斑块,衰老的内皮细胞和老化的大动脉中,REDD1的表达被上调.
- 通过siRNA介导的REDD1抑制改善了DG诱导的内皮细胞衰老,并减少了ROS积累.
- 作为抗氧化剂的NAC治疗降低了ROS,也降低了REDD1,这表明在内皮细胞衰老中REDD1和ROS之间存在正反循环.
- REDD1对ROS的调节与TXNIP-REDD1相互作用有关.
结论:
- REDD1促进内皮细胞衰老和氧化应激,可能通过抑制TXNIP介导的途径.
- 在动脉样硬化的进展中,REDD1发挥着重要作用.
- 向REDD1可能通过减轻内皮细胞衰老和氧化应激来代表动脉样硬化的一种新型治疗方法.
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