ArticleJournal of cellular and molecular medicine2019
Enhanced ROBO4 is mediated by up-regulation of HIF-1α/SP1 or reduction in miR-125b-5p/miR-146a-5p in diabetic retinopathy.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Emerging innovations in ophthalmic drug delivery for diabetic retinopathy: a translational perspective.Drug delivery and translational research · 2026Review
- From DNA Repair to Redox Signaling: The Multifaceted Role of APEX1 (Apurinic/Apyrimidinic Endonuclease 1) in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution.Cell death & disease · 2024Article
- Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions.International journal of molecular sciences · 2024Review
- Recent advances in the treatment and delivery system of diabetic retinopathy.Frontiers in endocrinology · 2024Review
- EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells.Frontiers in immunology · 2024Article
- Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats.International journal of ophthalmology · 2024Article
- The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy.Journal of translational medicine · 2023Article
- Identification of key ferroptosis genes in diabetic retinopathy based on bioinformatics analysis.PloS one · 2023Article
- Association of MicroRNA-146a with Type 1 and 2 Diabetes and their Related Complications.Journal of diabetes research · 2023Review
- Article
- Genetic variants of the hypoxia-inducible factor 3 alpha subunit (Hif3a) gene in the Fat and Lean mouse selection lines.Molecular biology reports · 2022Article
- Binding and Efficacy of Anti-Robo4 CAR-T Cells against Solid Tumors.Biomedicines · 2022Article
- LncRNA THRIL promotes high glucose-induced proliferation and migration of human retina microvascular endothelial cells through enhancing autophagy.Acta diabetologica · 2022Article
- Inhibitory effect of miR‑182‑5p on retinal neovascularization by targeting angiogenin and BDNF.Molecular medicine reports · 2022Article
- miRNA signatures in diabetic retinopathy and nephropathy: delineating underlying mechanisms.Journal of physiology and biochemistry · 2022Review
- The pathophysiological mechanisms underlying diabetic retinopathy.Frontiers in cell and developmental biology · 2022Review
- DNMT1-Mediated DNA Methylation Targets CDKN2B to Promote the Repair of Retinal Ganglion Cells in Streptozotocin-Induced Mongolian Gerbils during Diabetic Retinopathy.Computational and mathematical methods in medicine · 2022Article
- MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS.Journal of translational medicine · 2021Article
- MicroRNAs may provide new strategies in the treatment and diagnosis of diabetic retinopathy: Importance of VEGF.Iranian journal of basic medical sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinal cell damage caused by diabetes leads to retinal microvascular injury. Roundabout 4 (ROBO4) is involved in angiogenesis, which varies with the development of diabetic retinopathy (DR). Here, we explored the transcriptional regulation and microRNA-mediated modulation of ROBO4 expression and related retinal cell function in DR. A streptozotocin-induced type I diabetic animal model was established to detect the expression of hypoxia inducible factor-1α (HIF-1α), specificity protein 1 (SP1) and ROBO4. Retinal pigment epithelium (RPE) cells were cultured under hyperglycaemia or hypoxia and used for mechanistic analysis. Furthermore, roles of miR-125b-5p and miR-146a-5p were evaluated, and their targets were identified using luciferase assays. The cell functions were evaluated by MTS assays, permeability analysis and migration assays. The development of DR increased the levels of HIF-1α, SP1 and ROBO4 both in the DR model and in hyperglycaemic/hypoxic RPE cells. They were co-expressed and up-regulated in diabetic retinas and in RPE cells under hyperglycaemia/hypoxia. Knockdown of HIF-1α significantly inhibited SP1 and ROBO4, whereas SP1 down-regulation abolished ROBO4 expression in RPE cells under hyperglycaemia/hypoxia. miR-125b-5p and miR-146a-5p were down-regulated by hyperglycaemia and/or hypoxia. Up-regulation of miRNAs reversed these changes and resulted in recovery of target gene expression. Moreover, luciferase assays confirmed miR-125b-5p targeted SP1 and ROBO4, and miR-146a-5p targeted HIF-1α and ROBO4 directly. The decreased cell viability, enhanced permeability, and increased cell migration under DR conditions were mitigated by knockdown of HIF-1α/SP1/ROBO4 or up-regulation of miR-125b-5p/miR-146a-5p. In general, our results identified a novel mechanism that miR-125b-5p/miR-146a-5p targeting HIF-1α/SP1-dependent ROBO4 expression could retard DR progression.
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