miR-205-5p Modulates High Glucose-Induced VEGFA Levels in Diabetic Mice and ARPE-19 Cells.

IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Antioxidants Pub Date : 2025-02-14 DOI:10.3390/antiox14020218
María Ybarra, Miriam Martínez-Santos, Maria Oltra, María Muriach, Maria E Pires, Chiara Ceresoni, Javier Sancho-Pelluz, Jorge M Barcia
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Abstract

High glucose levels may cause vascular alterations in patients with diabetes, which can lead to complications such as diabetic retinopathy-an abnormal growth of retinal blood vessels. The micro-RNA miR-205-5p is known to regulate angiogenesis by modulating the expression of the vascular endothelial growth factor (VEGFA) in different systems. This study investigates the role of miR-205-5p in controlling VEGFA expression both in vitro and in the eye under hyperglycemic conditions. An alloxan-induced diabetic mouse model and retinal pigment epithelium human cell line (ARPE-19) were exposed to high glucose and treated with an ectopic miR-205-5p mimic. VEGFA mRNA and protein levels were assessed using qRT-PCR, Western blot, and immunocytochemistry. Additionally, human umbilical vein endothelial cells (HUVECs) were employed to evaluate angiogenesis. Our results show that high glucose significantly reduced miR-205-5p levels while upregulating VEGFA expression in both ARPE-19 cells and diabetic mice. The ectopic administration of miR-205-5p (via transfection or intravitreal injection) restored VEGFA levels and inhibited angiogenesis in HUVEC cultures. Based on these preliminary data, we suggest a potential therapeutic strategy against VEGFA involving miR-205-5p in proliferative eye-related vascular disorders.

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miR-205-5p调节糖尿病小鼠和ARPE-19细胞中高糖诱导的VEGFA水平
高血糖水平可能会导致糖尿病患者的血管改变,从而导致糖尿病视网膜病变等并发症——视网膜血管的异常生长。已知微rna miR-205-5p通过调节血管内皮生长因子(VEGFA)在不同系统中的表达来调节血管生成。本研究探讨了miR-205-5p在体外和高血糖条件下眼睛中控制VEGFA表达的作用。将四氧嘧啶诱导的糖尿病小鼠模型和视网膜色素上皮人细胞系(ARPE-19)暴露于高糖环境中,并用异位miR-205-5p模拟物处理。采用qRT-PCR、Western blot和免疫细胞化学检测VEGFA mRNA和蛋白水平。此外,人脐静脉内皮细胞(HUVECs)被用来评估血管生成。我们的研究结果表明,在ARPE-19细胞和糖尿病小鼠中,高糖显著降低miR-205-5p水平,同时上调VEGFA表达。异位给药miR-205-5p(通过转染或玻璃体内注射)恢复vefa水平并抑制HUVEC培养物中的血管生成。基于这些初步数据,我们提出了一种针对涉及miR-205-5p的VEGFA治疗增殖性眼部相关血管疾病的潜在治疗策略。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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