通过降低NHE1表达的调节,SGLT2抑制剂可以防止LPS诱导的M1巨分化,并缓解炎症性肠病
Ye Jin Kim1,2, Jonghwa Jin1, Dong-Ho Kim3
1Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-Ro, Jung-Gu, Daegu, 41944, Republic of Korea.
概括
-葡萄糖共运输体2 (SGLT2) 抑制剂通过降低NHE1和NCX1.1的调节来抑制M1巨细胞极化. 这种新的策略显示出治疗炎症性肠病 (IBD) 和其他M1巨介导的炎症状况的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢性疾病 代谢性疾病
背景情况:
- 经典激活的M1巨细胞通过糖解和细胞因子分泌驱动炎症性疾病,如炎症性肠病 (IBD).
- -葡萄糖共载体2 (SGLT2) 抑制剂对心肌细胞中的离子运输 (NHE1,NCX1) 和产生影响.
- 目前尚不清楚SGLT2抑制剂在通过NHE1和NCX1调节M1巨分化中的作用.
研究的目的:
- 调查SGLT2抑制剂是否可以通过向NHE1和NCX1.1来调节M1巨分化.
- 探索SGLT2抑制剂对巨细胞代谢和炎症反应的作用的潜在机制.
- 在炎症性肠病模型中评估SGLT2抑制剂的治疗潜力.
主要方法:
- 用脂多糖 (LPS) 刺激的小鼠骨髓衍生和腹腔内巨细胞中细胞反应的分析.
- 评估SGLT2抑制剂对NHE1和NCX1表达和活性的影响.
- 利用硫酸德克斯盐诱导大肠炎的小鼠模型来模仿炎症性肠病.
主要成果:
- 在LPS治疗的巨细胞中,NHE1和NCX1的过度表达与M1极化和通过PI3K/AKT/mTORC1信号的增强糖解相关.
- SGLT2 抑制剂有效抑制了 NHE1 和 NCX1 的表达和活性,导致 PI3K/AKT/mTORC1 信号和糖解减少.
- SGLT2 抑制剂在抑制M1两极化和细胞因子产生方面表现出有效性,在体外,体外和临床前IBD模型中.
结论:
- Na+/H+交换器1 (NHE1) 在促进M1巨细胞两极分化方面发挥着至关重要的作用.
- SGLT2 抑制剂代表了一种新的治疗策略,用于管理M1巨介导的炎症性疾病,包括炎症性肠病 (IBD).
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