APOL1促进了除质细胞之外的内皮细胞激活
Miguel Carracedo1, Elke Ericson2, Rasmus Ågren3
1Bioscience Renal, Research and Early Development, Cardiovascular , Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
iScience
|May 30, 2023
概括
高风险的Apolipoprotein L1 (APOL1) 基因变异可能通过激活脏内皮细胞 (ECs) 来驱动慢性病 (CKD). 这种激活会增加单细胞的粘附,这表明CKD病变发生的新机制.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 血管生物学 血管生物学
- 遗传学 是一个遗传学.
背景情况:
- 阿波利波蛋白L1 (APOL1) 高风险基因型与西非血统个体的慢性病 (CKD) 有关.
- 内皮细胞 (ECs) 在CKD病变发生过程中起着至关重要的作用.
- 通过APOL1影响CKD中EC的特定机制仍然不完全理解.
研究的目的:
- 调查APOL1高风险基因型是否通过 ECs的内在激活和功能障碍导致CKD.
- 为了确定分子通路和细胞变化与APOL1表达相关的脏ECs.
主要方法:
- 脏组织的单细胞RNA测序 (scRNA-seq) 分析来自脏精密医学项目.
- 来自患有CKD和APOL1表达的转基因小鼠的非裔美国人的公共数据集的转录组分析.
- 在体外研究中使用人类诱导的多能干细胞衍生的EC和具有APOL1表达的质EC.
主要成果:
- 在EC中检测到APOL1表达在各种脏血管区.
- 确定了一种EC激活特征,其特征是细胞间粘附分子1 (ICAM-1) 的增加和白细胞迁移通路的丰富.
- 在体外,APOL1的表达增加了ICAM-1和PECAM-1的表达,导致单细胞对ECs的附着增强.
结论:
- 在多个血管床中,APOL1似乎诱导了EC激活.
- 这种EC激活,涉及增加ICAM-1和单细胞粘附,可能是导致CKD的关键机制.
- APOL1对ECs的影响可能超出质血管系统,影响脏的整体健康.
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