异常的STING激活促进了巨细胞衰老,通过抑制糖尿病血管衰老中的自细胞衰老
Huiqing Ding1, Quan Zhang1, Rukai Yang1
1Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
iScience
|January 21, 2025
概括
糖尿病血管衰老涉及巨细胞衰老,由SASP恶化. 刺激激活通过抑制自而加速这一过程,为糖尿病并发症提供了新的治疗点.
科学领域:
- 细胞衰老 细胞衰老
- 血管生物学 血管生物学
- 免疫代谢过程中的免疫代谢.
背景情况:
- 糖尿病血管衰老是糖尿病的一个重要并发症.
- 大细胞衰老及其相关的分泌表型 (SASP) 导致血管功能障碍.
- 在糖尿病中巨细胞衰老中的STING的作用仍然不清楚.
研究的目的:
- 在2型糖尿病的背景下,研究STING在巨衰老中的作用.
- 阐明在糖尿病血管衰老中链接STING,自和衰老的分子机制.
- 评估针对STING-自轴的治疗潜力.
主要方法:
- 使用了2型糖尿病小鼠模型 (链毒素和高脂肪饮食).
- 评估了血管衰老标志物和衰老的巨细胞 *in vivo* 和 *in vitro*.
- 通过检查ULK1酸化和使用药理学调制剂 (H-151,DMXAA) 来研究STING-自途径.
主要成果:
- 高葡萄糖诱导巨细胞衰老,这反过来又促进了共同培养的血管光滑肌细胞的衰老.
- 发现STING激活通过在S757酸化ULK1,从而加速衰老来抑制自.
- 药理上抑制STING (H-151) 降低了衰老,而STING激动性 (DMXAA) 增强了衰老.
结论:
- 针-自轴是糖尿病血管衰老中巨细胞衰老的关键驱动因素.
- 通过通过ULK1酸化抑制自,STING激活促进衰老.
- 准STING-自途径为缓解糖尿病血管并发症提供了一个有希望的治疗策略.
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