内皮塞斯特林2协调多种保护途径,以维持糖尿病相关的内皮功能障碍的血管功能
Muhammad Ammar Zahid1, Aijaz Parray2, Hassaan Anwer Rathore1
1Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.
International journal of molecular sciences
|December 11, 2025
概括
塞斯特林2 (SESN2) 通过在甲基醇 (MGO) 压力下维持细胞功能来保护糖尿病患者的血管. 过度表达SESN2可以保持细胞活动,而沉默会使损伤恶化,突出显示SESN2.
科学领域:
- 内分泌学和新陈代谢学
- 细胞生物学 细胞生物学
- 血管生物学 血管生物学
背景情况:
- 糖尿病导致广泛的血管并发症,导致高死亡率.
- 甲基醇 (MGO) 是一种葡萄糖分解的副产品,对糖尿病人血管功能障碍有显著的贡献.
- 塞斯特林2 (SESN2) 是细胞应激反应的关键调节剂,但其在糖尿病内皮细胞中的作用尚不清楚.
研究的目的:
- 为了研究Sestrin2 (SESN2) 在维护内皮细胞血管功能中的功能,在甲基酸盐 (MGO) 诱导的压力下.
- 阐明SESN2在糖尿病情况下影响细胞平衡和血管健康的分子机制.
主要方法:
- 在EA.hy926内皮细胞中利用了功能丧失和功能增益的方法.
- 在MGO压力下评估内皮细胞血管生成能力,增殖和侵入性潜力.
- 分析了NRF2/HO-1,VEGF-C,AKT/mTOR和MAPK信号通路的参与.
主要成果:
- 在MGO压力下,SESN2过度表达保留了内皮细胞血管生成,增殖和入侵.
- 沉默SESN2加剧了MGO诱导的血管生成能力受损.
- SESN2激活了NRF2/HO-1抗氧化途径,增强了VEGF-C表达,平衡了AKT/mTOR信号,并减少了p38/ERK1/2的激活.
结论:
- 在MGO诱导的压力下,SESN2是内皮细胞恒温和血管生成的关键调节者.
- 在抗氧化途径和血管生成上SESN2的双重作用表明糖尿病血管并发症的治疗潜力.
- 针对SESN2可能提供一种新的策略,以改善糖尿病患者的治疗结果.
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