高葡萄糖通过调节miRNAlet7d-5p水平来促进动脉样硬化
Hua Wang1, Fentao Liu2, Wenyu Zhao3
1Department of Ultrasonography, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang City, Henan Province, China.
Journal of diabetes investigation
|March 14, 2024
概括
在糖尿病相关动脉样硬化中,微RNA let-7d-5p 的下调. 增加let-7d-5p水平可能会抑制血管光滑肌肉细胞的增殖和迁移,可能减缓动脉样硬化的进展.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 糖尿病并发症 糖尿病并发症
背景情况:
- 动脉样硬化 (AS) 是糖尿病的一个常见并发症.
- 微RNA let-7d-5p (let7d-5p) 表达在与糖尿病相关的AS中发生变化.
- 莱特7d-5p在AS病变发生过程中的确切作用尚不清楚.
研究的目的:
- 研究let7d-5p在糖尿病相关动脉样硬化中的作用.
- 阐明let7d-5p影响血管光滑肌细胞 (VSMCs) 的分子机制.
- 探索GLP-1受体激动剂 (GLP-1RA) 对let7d-5p水平和AS的潜在治疗作用.
主要方法:
- 定量逆转录-聚合酶连锁反应 (qRT-PCR) 来评估在人类大动脉斑块和VSMC中的let7d-5p表达.
- 实验室功能增益和丧失研究,以评估let7d-5p调制对VSMC增殖和迁移的影响.
- 机制研究以确定受let7d-5p影响的下游目标和信号通路,包括GSK3β/β-catenin通路和HMGA2 mRNA.
主要成果:
- 在糖尿病患者的动脉斑块和在高葡萄糖条件下的VSMC中观察到较低的let7d-5p表达.
- 过度表达let7d-5p抑制了VSMC的增殖和迁移,而抑制let7d-5p则促进了这些过程.
- 发现let7d-5p通过准HMGA2mRNA来激活GSK3β/β-catenin信号通路.
- 利拉格卢提德是一种GLP-1RA,增加了let7d-5p水平,从而抑制了VSMC的迁移和扩散.
结论:
- 高葡萄糖通过let7d-5p/HMGA2/GSK3β/β-catenin通路促进VSMC的增殖和迁移.
- 利拉格卢提德可以通过上调let7d-5p水平,对动脉样硬化产生保护作用.
- let7d-5p代表了治疗糖尿病相关动脉样硬化的潜在治疗标.
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