载有MiR-29a的纳米粒子通过Sgk1/Foxo3a轴缓解炎症性肠道疾病
Jintong Niu1, Junjie Zhu2, Zhilei Li3
1Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, PR China.
概括
携带微RNA-29a (LDH@miR-29a) 的双层氧化纳米粒子有效治疗炎症性肠病 (IBD). 这种新的方法通过准Sgk1和FoxO信号通路,同时减少炎症和纤维化.
科学领域:
- 生物医学工程
- 纳米技术
- 分子生物学
背景情况:
- 炎症性肠病 (IBD) 是一种慢性自身免疫性疾病,其全球发病率不断增加,其特征是严重的并发症和残疾.
- 微RNA-29a (miR-29a) 在调节炎症和纤维化方面具有潜力,但其治疗应用受到目标识别和传递载体挑战的阻碍.
- 层状双 (LDH) 具有免疫抑制性质,并作为微RNA的有效载体.
研究的目的:
- 开发和评估LDH@miR-29a作为治疗IBD的双重作用药物.
- 研究LDH@miR-29a的抗炎和抗纤维机制.
- 通过LDH@miR-29a调节的分子目标和信号通路.
主要方法:
- 在LDH中封装miR-29a以创建LDH@miR-29a纳米复合体.
- 在体外研究中评估了LDH@miR- 29a在用脂多糖 (LPS) 刺激的巨细胞中抑制炎症因子和反应性氧物种的疗效.
- 在用转化生长因子-β1 (TGF-β1) 治疗的NIH- 3T3细胞中评估了抗纤维作用.
- 转录组测序用于识别目标基因和信号通路.
- 在体内研究中使用大肠炎和肠纤维化的小鼠模型来评估治疗结果.
主要成果:
- 与单独使用LDH相比,LDH@ miR- 29a的传染效率提高,组织停留时间延长.
- 在LPS刺激的巨细胞中显著抑制炎症因子和反应性氧物种.
- 在用LDH@miR-29a治疗的细胞中,TGF-β1的亲纤维效应降低了.
- 转录组分析显示,LDH@miR-29a降低了Sgk1的调节,并促进了Foxo3a的核定位,将Sgk1确定为miR-29a的目标.
- 在小鼠模型中,用LDH@miR-29a治疗改善了结肠炎和肠纤维化.
结论:
- LDH@miR-29a是一个有前途的纳米药物输送系统用于IBD治疗.
- 通过Sgk1和FoxO信号通路的调节来促进联合的抗炎和抗纤维作用.
- 这项研究通过利用LDH和miR-29a的协同特性,为IBD的同时治疗提供了一个新的策略.
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