Yu Yongzhen, Zhang Mengyi, Zhou Wenjie, Yu Yangyang, Jian Liulian, Zou Yuping, Pang Long, Zou Xiulan
Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Department of Ophthalmology, General Hospital of Southern Theatre Command of PLA, Guangzhou, 510010, China.
Department of Ophthalmology, General Hospital of Southern Theatre Command of PLA, Guangzhou, 510010, China.
Exp Eye Res. 2025 Feb;251:110212. doi: 10.1016/j.exer.2024.110212. Epub 2024 Dec 17.
Diabetes mellitus (DM) is always accompanied by various complications, where diabetic retinopathy was a serious microvascular complications threatening the visual function of patients. This study evaluated the significance of miR-151a-5p and its effect on DR progression aiming to explore a novel biomarker for disease screening and monitoring. Study enrolled 137 patients with DM and 103 diabetes patients with DR. Serum miR-151a-5p was compared with PCR, and its clinical significance was evaluated from the perspectives of diagnosis and severity prediction. High-glucose-treated human retinal cell model was established, the effect of miR-151a-5p on high-glucose-induced cell injury was assessed based on cell growth, inflammation, oxidative stress, and endoplasmic reticulum stress. In mechanism, the downstream targets of miR-151a-5p were predicted, based on the function enrichment, the involvement of DKK3 and the MAPK signaling was estimated. Increasing miR-151a-5p was identified as a risk factor for DR in DM patients diagnosing DR patients and was positively correlated with disease severity predicting severe development of DR. Silencing miR-151a-5p alleviated high-glucose-induced reducing proliferation, activated inflammation, oxidative stress, and endoplasmic reticulum stress in human retinal cells. Negative regulation of DKK3 by miR-151a-5p was observed, and the knockdown of DKK3 could reversed the protective effect of miR-151a-5p. High-glucose activate the MAPK signaling, which was suppressed by the miR-151a-5p/DKK3 axis, and MAPK signaling was demonstrated to mediate the functional role of the miR-151a-5p/DKK3 axis. miR-151a-5p can be considered as a biomarker for the onset and progression of DR. miR-151a-5p potentially modulates the progression of DR through regulating inflammation, oxidative stress, and endoplasmic reticulum stress via the MAPK signaling.
糖尿病（DM）常伴有各种并发症，其中糖尿病视网膜病变是一种严重的微血管并发症，威胁着患者的视觉功能。本研究评估了miR-151a-5p的意义及其对糖尿病视网膜病变进展的影响，旨在探索一种用于疾病筛查和监测的新型生物标志物。研究纳入了137例糖尿病患者和103例糖尿病视网膜病变患者。采用聚合酶链反应（PCR）比较血清miR-151a-5p，并从诊断和严重程度预测的角度评估其临床意义。建立高糖处理的人视网膜细胞模型，基于细胞生长、炎症、氧化应激和内质网应激评估miR-151a-5p对高糖诱导的细胞损伤的影响。在机制方面，预测了miR-151a-5p的下游靶点，基于功能富集，评估了DKK3和丝裂原活化蛋白激酶（MAPK）信号通路的参与情况。在诊断糖尿病视网膜病变患者时，miR-151a-5p升高被确定为糖尿病患者发生糖尿病视网膜病变的危险因素，且与疾病严重程度呈正相关，提示糖尿病视网膜病变的严重进展。沉默miR-151a-5p可减轻高糖诱导的人视网膜细胞增殖减少、炎症激活、氧化应激和内质网应激。观察到miR-151a-5p对DKK3的负调控作用，敲低DKK3可逆转miR-151a-5p的保护作用。高糖激活MAPK信号通路，而miR-151a-5p/DKK3轴可抑制该通路，且MAPK信号通路介导了miR-151a-5p/DKK3轴的功能作用。miR-151a-5p可被视为糖尿病视网膜病变发生和进展的生物标志物。miR-151a-5p可能通过MAPK信号通路调节炎症反应、氧化应激和内质网应激，从而潜在地调节糖尿病视网膜病变的进展。
