Zhao Jianyu, Sun Zewen, Li Zimeng, Xu Mengyu, Tian Aowen, An Zhengwen, Guo Wenbo, He Chang, Dong Ying, Wen Jianping, Yang Jianli, Wang Qing, Chen Peng
Department of Endocrinology, China-Japan Union Hospital, Jilin University, Changchun, China.
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, China.
Diabetes Obes Metab. 2025 Apr;27(4):1888-1901. doi: 10.1111/dom.16182. Epub 2025 Jan 7.
This study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).
This study employed a case-control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health. An integrative approach combining single-cell sequencing data from mouse and rat models was used to explore the molecular mechanism in retinal cells under diabetes condition.
We identified a specific set of circulating microRNAs with strong predictive potential for distinguishing NPDR patients. In addition, a novel microRNA targeting the ETS proto-oncogene 1 (Ets1), a key regulator of microvascular angiogenesis, was found to be upregulated in the plasma of NPDR patients. Analysis of single-cell sequencing data suggested that Ets1 expression was downregulated in diabetic endothelial cells and was associated with the repression of Angiopoietin-1 and phosphoinositide 3-kinase-Akt (PI3K-Akt) signalling pathways, indicating an anti-angiogenic mechanism in NPDR.
The identification of a novel microRNA involved in the anti-angiogenic mechanism in NPDR provides new insights into the molecular underpinnings of endothelial dysfunction in diabetic retinopathy. Our retina-specific circulating microRNA panel has potential utility in risk assessment and early detection of NPDR.
本研究旨在发现非增殖性糖尿病视网膜病变（NPDR）中促成血管生成的调控机制。
本研究采用病例对照设计，纳入患有和未患有NPDR的2型糖尿病患者。我们利用微小RNA测序分析2型糖尿病患者的血浆和视网膜样本，以鉴定与视网膜健康相关的已知和新型微小RNA。采用整合小鼠和大鼠模型单细胞测序数据的方法，探索糖尿病状态下视网膜细胞的分子机制。
我们鉴定出一组对区分NPDR患者具有强大预测潜力的特定循环微小RNA。此外，发现一种靶向ETS原癌基因1（Ets1）（微血管生成的关键调节因子）的新型微小RNA在NPDR患者血浆中上调。单细胞测序数据分析表明，Ets1在糖尿病内皮细胞中的表达下调，且与血管生成素-1和磷酸肌醇3激酶-蛋白激酶B（PI3K-Akt）信号通路的抑制有关，提示NPDR中存在抗血管生成机制。
鉴定出参与NPDR抗血管生成机制的新型微小RNA，为糖尿病视网膜病变中内皮功能障碍的分子基础提供了新见解。我们的视网膜特异性循环微小RNA检测 panel 在NPDR的风险评估和早期检测中具有潜在应用价值。
