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单细胞分析确定MKI67+微质细胞是增殖性糖尿病视网膜病变中新血管化的驱动因素

Keyi Zou¹, Xue Li¹, Bibo Ren²

¹Department of Ophthalmology, The Third Hospital Affiliated to the Third Military Medical University Department of Ophthalmology, Chongqing, 400042, China.

Journal of translational medicine

|March 12, 2025

概括

研究人员确定了MKI67+微质,这是一种与乳酸代谢和增殖相关的新型细胞类型,在增殖性糖尿病视网膜病变 (PDR) 新血管化中起着关键作用. 在小鼠模型中,Abemaciclib治疗减少了这种病理性血管生长.

科学领域:

眼科和视觉科学眼科和视觉科学
细胞生物学和代谢
糖尿病并发症研究研究糖尿病并发症

背景情况:

增殖性糖尿病视网膜病变 (PDR) 是糖尿病相关失明的主要原因.
乳酸盐水平升高是PDR预后的一个关键生物标志物.
连接乳酸与PDR新血管化的途径尚未完全理解.

研究的目的:

在PDR中识别和表征乳酸相关细胞类型.
研究这些细胞在病理性新血管化的作用.
探索PDR的潜在治疗点.

主要方法:

单细胞RNA测序 (scRNA-seq) 用于识别与PDR相关的细胞类型.
对基因表达和与乳酸代谢相关的分子通路的分析.
在高葡萄糖条件下进行体外微质细胞培养.
在体内氧气诱导视网膜病变 (OIR) 的小鼠模型用abemaciclib.lib治疗.

主要成果:

发现了一种新的微质子集,MKI67+微质,乳酸代谢和增殖基因的高表达 (MKI67,PARK7,LDHA).
MKI67+微质细胞通过SPP1-ITGA4与内皮细胞进行信号传递来促进血管生成.
高葡萄糖刺激了微质乳酸代谢和血管增殖 in vitro.
在OIR小鼠模型中,Abemaciclib显著降低了视网膜新血管化.

结论:

MKI67+微质细胞是一种新型细胞类型,与PDR中的乳酸代谢密切相关.
这一发现为PDR病原和代谢动态提供了新的见解.
这些结果表明针对PDR的向治疗策略的潜力.

关键词:

阿贝马西克利布 (Abemaciclib) 是一个有着乳酸代谢基因乳酸代谢基因微质细胞中的微质细胞氧气诱导的视网膜病变是由氧气引起的.扩散性糖尿病视网膜病变一个单细胞分析.

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