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在糖尿病中,NRF2-HIF2α信号减弱了内皮细胞衰老,并维持了细胞间连接

Jian Shen^1,2,3,4, Yifan Lai⁵, Yaner Lu^1,2,3,4

¹Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

International journal of biological sciences

|August 8, 2024

概括

糖尿病会损害内皮细胞,导致衰老和结合问题. NRF2和HIF-2α可以防止轻度高血糖,但奥尔蒂普拉兹是需要严重的高血糖症,为血管损伤提供潜在的治疗方法.

科学领域:

内分泌学在内分泌学.
细胞生物学细胞生物学
血管生物学血管生物学

背景情况:

糖尿病与内皮功能障碍有关,其特征是细胞间结节受损和细胞衰老加速.
糖尿病引起的内皮损伤的潜在分子机制和有效的治疗干预措施尚未完全理解.

研究的目的:

阐明内皮细胞 (HUVEC) 抵消衰老并在高血糖条件下保持结合完整性的机制.
确定潜在的治疗策略,以减轻与糖尿病相关的血管内皮损伤.

主要方法:

研究了NRF2乙化和NRF2-HIF-2α相互作用在不同葡萄糖度 (10mM,15mM,25mM) 下HUVEC中的作用.
评估了NRF2激活剂Oltipraz对HUVEC衰老和严重高血糖症下细胞间结合完整性的影响.
分析了基因转录 (GST,SOD1,GPX1) 和蛋白质相互作用 (NRF2,HIF-2α,奥克卢丁,E-cadherin).

主要成果:

通过NRF2乙化和NRF2-HIF-2α核相互作用,HUVECs减轻衰老,并通过NRF2乙化和NRF2-HIF-2α核相互作用在中度高血糖 (10-15mM) 下保持结合完整性,减少氧化应激.
这些保护机制在严重高血糖 (25mM) 的情况下是不够的.
通过调节NRF2和HIF-2α,奥利普拉兹治疗显著降低HUVEC衰老,并通过调节NRF2和HIF-2α,在严重高血糖症下保留细胞间接点.

结论:

NRF2乙化和核NRF2-HIF-2α相互作用是对中度糖尿病内皮功能障碍的关键保护机制.
奥尔蒂普拉兹通过同时向NRF2和HIF-2α来证明治疗潜力,有效地对抗内皮细胞的严重高血糖损伤.
奥尔蒂普拉兹是治疗糖尿病引起的血管损伤的有希望的候选人,包括动脉样硬化和膜化.

关键词:

这就是HIF-2α.这就是NRF2的NRF2.奥尔蒂普拉兹 (Oltipraz) 是一个古老的城市.糖尿病糖尿病患者糖尿病患者细胞间结点细胞间结点衰老是一种老化.

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