ArticleJournal of diabetes research2014
Hyperglycemia induces Toll-like receptor-2 and -4 expression and activity in human microvascular retinal endothelial cells: implications for diabetic retinopathy.
Article in Journal of diabetes research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 108 citations in OpenAlex.
- Systemic-retinal inflammatory crosstalk in diabetic macular edema: correlation between hematologic indices and macular OCT-features.International journal of retina and vitreous · 2026Article
- Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.International journal of molecular sciences · 2023Review
- Review
- Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy.Neural regeneration research · 2023Review
- Review
- The Metaflammatory and Immunometabolic Role of Macrophages and Microglia in Diabetic Retinopathy.Human cell · 2021Review
- Interaction of miR-146a-5p with oxidative stress and inflammation in complications of type 2 diabetes mellitus in male rats: Anti-oxidant and anti-inflammatory protection strategies in type 2 diabetic retinopathy.Iranian journal of basic medical sciences · 2021Article
- Loss of TLR4 in endothelial cells but not Müller cells protects the diabetic retina.Experimental eye research · 2021Article
- MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4.Experimental & molecular medicine · 2021Article
- Lysophosphatidylcholine Offsets the Protective Effects of Bone Marrow Mesenchymal Stem Cells on Inflammatory Response and Oxidative Stress Injury of Retinal Endothelial Cells via TLR4/NF-Journal of immunology research · 2021Article
- Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy.Journal of inflammation research · 2021Review
- Dihydrotanshinone, a Natural Diterpenoid, Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor.International journal of molecular sciences · 2020Article
- In vitro and ex vivo anti-diabetic and anti-hyperglycemic properties of Zataria multiflora essential oil.Molecular biology reports · 2020Article
- Role of HMGB1 signaling in the inflammatory process in diabetic retinopathy.Cellular signalling · 2020Review
- The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2020Review
- MD2 activation by direct AGE interaction drives inflammatory diabetic cardiomyopathy.Nature communications · 2020Article
- TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones.Biomolecules · 2020Article
- The Mechanism of Contrast-Induced Acute Kidney Injury and Its Association with Diabetes Mellitus.Contrast media & molecular imaging · 2020Review
- Toll-like Receptors as a Potential Drug Target for Diabetes Mellitus and Diabetes-associated Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Review
- Microglia and Inflammatory Responses in Diabetic Retinopathy.Frontiers in immunology · 2020Review
Corrections and comments
- Retraction · 2020-10-31Duplication of/in Image · Manipulation of Images · Upgrade/Update of Prior Notice(s) · · Uthra Rajamani has NIH finding of misconduct;
- Correction · 2016-11-14Duplication of/in Image · Error in Image · Updated to Retraction · · Uthra Rajamani has NIH finding of misconduct;
- Erratum issued
- Retracted
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic retinopathy (DR) causes visual impairment in working age adults and hyperglycemia-mediated inflammation is central in DR. Toll-like receptors (TLRs) play a key role in innate immune responses and inflammation. However, scanty data is available on their role in DR. Hence, in this study, we examined TLR2 and TLR4 mRNA and protein expression and activity in hyperglycemic human retinal endothelial cells (HMVRECs). HMVRECs were treated with hyperglycemia (HG) or euglycemia and mRNA and protein levels of TLR-2, TLR-4, MyD88, IRF3, and TRIF as well as NF-κB p65 activation were measured. IL-8, IL-1β, TNF-α and MCP-1, ICAM-1, and VCAM-1 as well as monocyte adhesion to HMVRECs were also assayed. HG (25 mM) significantly induced TLR2 and TLR4 mRNA and protein in HMVRECs. It also increased both MyD88 and non-MyD88 pathways, nuclear factor-κB (NF-κB), biomediators, and monocyte adhesion. This inflammation was attenuated by TLR-4 or TLR-2 inhibition, and dual inhibition by a TLR inhibitory peptide as well as TLR2 and 4 siRNA. Additionally, antioxidant treatment reduced TLR-2 and TLR4 expression and downstream inflammatory markers. Collectively, our novel data suggest that hyperglycemia induces TLR-2 and TLR-4 activation and downstream signaling mediating increased inflammation possibly via reactive oxygen species (ROS) and could contribute to DR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.