通过向NF-κB和AP-1通路,KDM2B调节了败血症的炎症和氧化应激
Xin Li1, Xinyu Tian1, Dongliang Zhang1
1Department of Nephrology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Immunity, inflammation and disease
|September 29, 2023
概括
氨酸特异性去甲基酶2B (KDM2B) 阻断通过减少炎症和氧化应激来防止败血症引起的急性损伤 (AKI). 这表明KDM2B是治疗毒症相关AKI的潜在治疗标.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 败血症研究 败血症研究
背景情况:
- 败血症经常导致急性损伤 (AKI),这是一个重大的临床挑战.
- 基因组蛋白修饰酶氨酸特异性去甲基酶2B (KDM2B) 与各种病理有关,但其在败血症诱导的AKI中的作用仍然未知.
研究的目的:
- 研究KDM2B在细胞活力,炎症和与败血症相关的AKI中氧化应激中的功能.
- 阐明KDM2B在败血症诱导的AKI中的作用中涉及的信号通路.
主要方法:
- 在实验室中使用脂聚糖 (LPS) 诱导的HK-2细胞创建了一种急性损伤 (AKI) 模型.
- 通过Western blot和qPCR分析了关键蛋白质和基因表达 (KDM2B,COX2,iNOS,NF-κB,AP-1通路组件).
- 细胞活力,细胞毒性 (LDH释放) 和炎症媒介的水平,氧化应激标志物 (TNF-α,IL-1β,IL-18,VCAM-1,SOD,MDA,GSH,H2O2),通过CCK-8试验和ELISA量化.
主要成果:
- 在LPS诱导的AKI中,KDM2B倒置显著改善了细胞活力,降低了细胞毒性和LDH释放.
- 减少KDM2B表达降低了促炎分子 (TNF-α,IL-1β,IL-18,VCAM-1) 的水平和转录.
- 通过增加抗氧化剂标记物 (SOD,GSH) 和减少氧化损伤标记物 (MDA,H2O2),KDM2B敲击减轻了氧化应激,同时也减少了COX2和iNOS的表达. NF-κB和AP-1通路的KDM2B激活与LPS诱导的HK-2细胞损伤有关.
结论:
- 在症诱导的AKI模型中,KDM2B敲除改善了细胞毒性,炎症和氧化应激.
- 抑制NF-κB和AP-1信号通路介导KDM2B敲击的保护作用.
- KDM2B代表了一种潜在的治疗点,用于管理与败血症相关的AKI.
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