综合性网络毒理学和单细胞转录组学揭示TP53是PCB诱导的微质功能障碍在糖尿病视网膜病变中的关键调解者
Mengjie Zhou1, Xiaofei Huang2, Luhao Wang3
1National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
Ecotoxicology and environmental safety
|February 25, 2026
概括
多双 (PCB) 通过激活TP53基因,恶化糖尿病视网膜病变 (DR),促进视网膜微质中的炎症. 减少PCB暴露可能有助于减缓DR进展.
科学领域:
- 环境毒理学环境毒理学
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
背景情况:
- 糖尿病视网膜病变 (DR) 是与代谢和环境因素相关的视力损失的主要原因.
- 聚二 (PCB) 是一种环境毒素,可能在DR病变发生过程中发挥作用.
研究的目的:
- 调查PCBs在糖尿病视网膜病变 (DR) 发展中的作用.
- 确定关键的分子点和涉及PCB诱导DR的途径.
主要方法:
- 网络毒理学用于在PCB和DR之间找到重叠的基因标.
- 机器学习可以改进核心基因 (TP53,ESR1,EGR1,HSPA5).
- 诊断建模,分子对接,单细胞RNA测序和体外细胞培养实验.
主要成果:
- TP53显示了DR的高诊断准确性 (NPDR的AUC为0.740,PDR的0.920) 并与疾病严重程度相关.
- PCBs强烈与TP53和ESR1结合;PCB暴露对微质中的TP53进行上调,导致炎症和M1两极分化.
- 抑制TP53降低了PCB诱导的微质激活和促炎性细胞因子分泌.
结论:
- PCBs通过一个TP53-依赖的通路加剧糖尿病视网膜病变 (DR),该通路激活促炎性微质细胞.
- TP53是缓解DR进展的关键生物标志物和潜在治疗标.
- 减少环境PCB暴露对于管理糖尿病视网膜病变至关重要.
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