针对 miR-6720-5p/CYB5R2 轴的 hsa_circ_0000047 可减轻糖尿病视网膜病变的炎症和血管生成。

IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Archives of Physiology and Biochemistry Pub Date : 2024-10-01 Epub Date: 2023-03-27 DOI:10.1080/13813455.2023.2190055
Lin Liao, Jinpeng Chen, Sheng Peng
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引用次数: 0

摘要

背景:糖尿病视网膜病变(DR)是糖尿病(DM)的常见并发症。环状 RNA(circRNA)通过调节炎症和血管生成,成为 DR 发生的关键调控因子:材料与方法:利用高糖(HG)诱导人视网膜微血管内皮细胞(hRMECs),在体外构建 DR 模型。采用定性实时聚合酶链反应(qRT-PCR)或免疫印迹法检测 DR 和 HG 诱导的 hRMECs 中 hsa_circ_0000047、miR-6720-5p 和 CYB5R2 的水平。细胞功能实验检测了 HG 诱导的 hRMECs 的活力、炎症、迁移、侵袭和血管生成的变化。结果:DR 中 hsa_circ_0000047 和 CYB5R2 下调,而 miR-6720-5p 上调。细胞功能实验表明,过表达 hsa_circ_0000047 可抑制 HG 诱导的 hRMECs 的活力、炎症、迁移、侵袭和血管生成。在机制方面,hsa_circ_0000047可以海绵状调节miR-6720-5p在hRMECs中的CYB5R2表达。此外,CYB5R2基因敲除可逆转hsa_circ_0000047过表达对HG诱导的hRMECs的影响:我们的研究揭示了 hsa_circ_0000047 通过靶向 miR-6720-5p/CYB5R2 轴减轻了 HG 诱导的 hRMECs 的炎症和血管生成,这可能是 DR 治疗的一种新型生物标记物。
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hsa_circ_0000047 targeting miR-6720-5p/CYB5R2 axis alleviates inflammation and angiogenesis in diabetic retinopathy.

Context: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). Circular RNAs (circRNAs) act as key regulators of DR development by regulating inflammation and angiogenesis.Objective: This study aimed to elucidate the function and mechanism of hsa_circ_0000047 in DR.Materials and methods: High glucose (HG) was used to induce human retinal microvascular endothelial cells (hRMECs) to construct a DR model in vitro. Qualitative real-time polymerase chain reaction (qRT-PCR) or western blotting were used to detected the levels of hsa_circ_0000047, miR-6720-5p, and CYB5R2 in DR and HG-indeced hRMECs. Cell functional experiments were performed to detect the change of viability, inflammation, migration, invasion, and angiogenesis of HG-induced hRMECs. Besides, the correlation between miR-6720-5p and hsa_circ_0000047/CYB5R2 was confirmed by luciferase assay and Pearson correlation analysis.Results: hsa_circ_0000047 and CYB5R2 were downregulated in DR, whereas miR-6720-5p was upregulated in DR. Cell functional experiments showed that hsa_circ_0000047 overexpression restrained viability, inflammation, migration, invasion, and angiogenesis of HG-induced hRMECs. Regarding mechanism, hsa_circ_0000047 could sponge miR-6720-5p to regulate CYB5R2 expression in hRMECs. Additionally, CYB5R2 knockdown reversed the effects of hsa_circ_0000047 overexpression on HG-induced hRMECs.Conclusion: Our study revealed that hsa_circ_0000047 alleviated inflammation and angiogenesis in HG-induced hRMECs by targeting the miR-6720-5p/CYB5R2 axis, which may be a novel biomarker for DR therapy.

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来源期刊
Archives of Physiology and Biochemistry
Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY
CiteScore
6.90
自引率
3.30%
发文量
21
期刊介绍: Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.
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