抑制糖辅运输体2增加了表皮生长因子的表达,并改善了2型糖尿病患者的治疗结果
Taha Sen1, Wenjun Ju2, Viji Nair3
1Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Kidney international
|August 5, 2023
概括
像卡纳格利弗洛辛这样的糖共运输体2 (SGLT2) 抑制剂可以通过增加尿表皮生长因子 (uEGF) - - 脏修复的因素 - - 来保护脏. 较低的uEGF表明2型糖尿病患者的病风险较高.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 糖共运输体2 (SGLT2) 抑制剂对脏的保护机制尚不完全理解.
- 尿表皮生长因子 (uEGF) 是一个关键的线粒体发生因子,涉及脏修复过程.
- 2型糖尿病 (T2D) 与病进展的风险增加有关.
研究的目的:
- 为了研究尿液EGF (uEGF) 水平和T2D患者的脏结果之间的关联.
- 阐明SGLT2抑制剂卡纳格利弗洛辛影响脏EGF表达的分子机制.
主要方法:
- 在3521名参与CANagliflozin心血管评估研究 (CANVAS) 的参与者中分析了uEGF与肌素的比率 (uEGF/Cr).
- 用多变量调整的考克斯回归模型来评估uEGF/Cr与结局之间的关联.
- 单细胞RNA测序是在T2D患者 (有或没有SGLT2抑制剂) 和健康对照者的脏活检组织上进行的.
主要成果:
- 在CANVAS研究中,较高的基线uEGF/Cr与结局风险降低有关.
- 卡纳格利弗洛辛治疗稳定了uEGF/Cr水平,而安慰剂导致了下降.
- 单细胞RNA测序显示,SGLT2抑制剂增加了组织中的EGF表达,特别是在厚厚的升环中,并将协同表达网络从内衣林-1转移到更健康的状态.
结论:
- 降低uEGF水平意味着T2D患者病进展的风险增加.
- 卡纳格利弗洛辛增强脏组织EGF表达,可能通过一种涉及管状修复和逆转损伤的机制.
- 在T2D中,EGF信号传递对SGLT2抑制剂的保护作用起着至关重要的作用.
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