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Bioengineered ; 12(1): 7508-7518, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34608841

RESUMO

Hsa_circ_0001850_circ_0001850 (circ-UBAP2) is reported to be upregulated in diabetic retinopathy (DR). However, its role in high glucose (HG)-triggered oxidative stress and vascular dysfunction in DR is unclear. This study aimed to investigate the potential of circUBAP2 in DR. The content of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were analyzed using the corresponding kits. Western blotting was performed to detect the protein expression of Nrf2, HO-1, and SOD-1. MTT assay was conducted to assess cell viability. A transwell migration assay was used to determine the migration ability of human retinal microvascular endothelial cells (hRMECs). A Matrigel tube formation assay was performed to analyze tube formation. The targeting relationships were verified using a luciferase reporter assay. We found that the circ-UBAP2 expression increased in DR patients and HG-treated hRMECs. Downregulation of circ-UBAP2 ameliorated HG-induced oxidative stress and dysfunction of hRMECs. Mechanistically, circ-UBAP2 sponges miR-589-5p, which is downregulated under hyperglycemic conditions. In addition, EGR1 was confirmed to be a target gene of miR-589-5p and was overexpressed in HG-treated hRMECs. In addition, EGR1 reversed the effects of miR-589-5p and induced oxidative stress and dysfunction in hRMECs. Taken together, knockdown of circ-UBAP2 relieved HG-induced oxidative stress and dysfunctions of the hRMECs through the miR-589-5p/EGR1 axis, which may offer a promising therapeutic target for DR.


Assuntos
Retinopatia Diabética/metabolismo , MicroRNAs/genética , Estresse Oxidativo/genética , RNA Circular/genética , Vasos Retinianos/citologia , Células Cultivadas , Regulação para Baixo/genética , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Endotélio Vascular/citologia , Glucose/efeitos adversos , Humanos , MicroRNAs/metabolismo , Neovascularização Patológica/induzido quimicamente , Neovascularização Patológica/genética , Estresse Oxidativo/efeitos dos fármacos , RNA Circular/metabolismo
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