ArticleEndocrine2019
Upregulated VEGF and Robo4 correlate with the reduction of miR-15a in the development of diabetic retinopathy.
Article in Endocrine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Slit2/Robo Signaling Restores Diabetic Erectile Function via Neurovascular Remodeling.Andrology · 2026Article
- KNG-1, HSPG and Robo4 reflect hypertension-driven subclinical renal alterations and provide incremental diagnostic value in type 2 diabetic nephropathy.Scientific reports · 2026Article
- Association of blood miR-15a, miR-146a and miR-200b levels with stages of diabetic retinopathy.Scientific reports · 2025Article
- Robo4 inhibits neovascularization in oxygen-induced retinopathy by regulating ARF6 and VEGF.Human cell · 2025Article
- Article
- Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution.Cell death & disease · 2024Article
- Gene augmentation for autosomal dominant retinitis pigmentosa using rhodopsin genomic loci nanoparticles in the P23HGene therapy · 2023Article
- The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy.Journal of translational medicine · 2023Article
- Inhibitory effect of miR‑182‑5p on retinal neovascularization by targeting angiogenin and BDNF.Molecular medicine reports · 2022Article
- Inhibition of KCTD10 Affects Diabetic Retinopathy Progression by Reducing VEGF and Affecting Angiogenesis.Genetics research · 2022Article
- MicroRNAs may provide new strategies in the treatment and diagnosis of diabetic retinopathy: Importance of VEGF.Iranian journal of basic medical sciences · 2021Review
- MicroRNA-34a promotes apoptosis of retinal vascular endothelial cells by targeting SIRT1 in rats with diabetic retinopathy.Cell cycle (Georgetown, Tex.) · 2020Article
- MiR-221/SIRT1/Nrf2 signal axis regulates high glucose induced apoptosis in human retinal microvascular endothelial cells.BMC ophthalmology · 2020Article
- Regulatory mechanisms of Robo4 and their effects on angiogenesis.Bioscience reports · 2019Review
- LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy.Frontiers in pharmacology · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeVascular endothelial growth factor (VEGF) plays implicated roles in diabetic retinopathy (DR). The role of roundabout 4 (Robo 4) in angiogenesis and vasculogenesis is controversial; however, the interdependent relationship between these two factors has not been studied in DR. This study determined the colocalization of VEGF and Robo4 in fibrovascular membranes (FVM) from patients with proliferative diabetic retinopathy (PDR). MicroRNA (miRNA)-mediated modulation of VEGF and Robo4 was explored in diabetic rats and ARPE-19 tissue culture cells under hyperglycemia.
methodsVEGF and Robo4 co-expression in the FVM was analyzed using immunofluorescence. VEGF and Robo4 levels were determined in diabetic retinas and ARPE-19 tissue culture cells under high glucose using western blotting and RT-qPCR. MicroRNA agomir was intraocularly injected to increase miR-15a expression and downregulate VEGF and Robo4 levels in diabetic retinas.
resultsVEGF and Robo4 colocalization in FVM vessels was observed. Increased VEGF levels were consistent in diabetic retinas and ARPE-19 tissue culture cells cultured under hyperglycemia. Robo4 decreased in ARPE-19 tissue culture cells exposed to hyperglycemia for 72 h, whereas it increased in diabetic rat retinas. Several miRNAs were differentially expressed during DR progression. Furthermore, miR-15a agomir injection inhibited high levels of VEGF and Robo4 in diabetic retinas.
conclusionsVEGF and Robo4 were co-expressed in FVMs from PDR patients. In the early stages of DR, VEGF was upregulated and contributed to DR development, whereas, in the late stage of DR, VEGF and Robo4 worked together to aggravate DR progression. However, miR-15a could downregulate VEGF and Robo4 to ameliorate DR development.
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