核素93限制了Yap活动,以防止内皮细胞衰老
Tung D Nguyen1,2, Mihir K Rao1, Shaiva P Dhyani1
1Department of Physiology and Biophysics, The University of Illinois at Chicago - College of Medicine, Chicago, Illinois, USA.
Aging cell
|February 13, 2024
概括
衰老会通过降低核素93 (Nup93) 水平来损害内皮细胞 (ECs),损害核运输,并导致血管衰老. 恢复Nup93可以防止EC衰老和炎症.
科学领域:
- 血管生物学 血管生物学
- 细胞衰老 细胞衰老
- 疾病的分子机制.
背景情况:
- 内皮细胞 (ECs) 对血管健康至关重要,易受衰老和炎症的影响.
- 正确的核孔综合体 (NPC) 功能对EC至关重要,但NPC的完整性随着年龄的增长而下降.
- 损伤的核细胞质运输与与年龄有关的EC功能障碍有关.
研究的目的:
- 调查核蛋白93 (Nup93) 在内皮细胞 (EC) 衰老和血管健康中的作用.
- 确定Nup93影响EC衰老和炎症的机制.
- 探索Nup93作为与年龄相关的血管疾病的潜在治疗点.
主要方法:
- 在老年小鼠血管系统和体外EC衰老模型中分析Nup93蛋白水平.
- 使用人类ECs进行体外研究,以评估Nup93损失和恢复的影响.
- 研究核细胞质运输,雅普局部化和炎症标志物表达.
- 药理干预措施来评估EC衰老中的Yap过活化.
主要成果:
- 在老年小鼠和老化EC中,内皮Nup93蛋白水平显著下降.
- 在EC中Nup93的损失会诱导衰老,促进炎症粘附分子,并损害NPC运输.
- 在老化的EC中恢复Nup93可以逆转老化的表型.
- 损失Nup93和衰老导致Yap核积累和下游炎症,Yap过度活化是关键的后果.
结论:
- 内皮质Nup93对于维持EC健康和预防血管衰老至关重要.
- 衰老通过减少内皮细胞Nup93来损害血管功能,导致NPC功能受损和EC衰老.
- 向内皮细胞Nup93代表了一种新的治疗策略,用于对抗与年龄相关的血管功能障碍.
关键词:
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