ArticleInvestigative ophthalmology & visual science2013
Effects of high glucose-induced Cx43 downregulation on occludin and ZO-1 expression and tight junction barrier function in retinal endothelial cells.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 85 citations in OpenAlex.
- Exosome-Biomaterial Platforms for Diabetic Skin Infections: Microenvironment Remodeling, Responsive Delivery, and Clinical Translation.International journal of nanomedicine · 2026Review
- Imeglimin Alleviates High-Glucose-Induced Bioenergetic and Oxidative Stress Thereby Enhancing Intercellular Adhesion in H9c2 Cardiomyoblasts.International journal of molecular sciences · 2025Article
- Impact of Estrogen on Purinergic Signaling in Microvascular Disease.International journal of molecular sciences · 2025Review
- Downregulation of connexin 43 is crucial for basal cell alignment in ameloblastoma and odontogenic keratocyst.The Saudi dental journal · 2024Article
- Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components.Cell & bioscience · 2024Review
- Article
- Therapeutic Delivery of Soluble Fractalkine Ameliorates Vascular Dysfunction in the Diabetic Retina.International journal of molecular sciences · 2024Article
- Single-Cell RNA Sequencing Reveals Transcriptional Signatures and Cell-Cell Communication in Diabetic Retinopathy.Endocrine, metabolic & immune disorders drug targets · 2024Article
- The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients.Frontiers in neuroscience · 2024Review
- Gap Junctions or Hemichannel-Dependent and Independent Roles of Connexins in Fibrosis, Epithelial-Mesenchymal Transitions, and Wound Healing.Biomolecules · 2023Review
- O-GlcNAcylation Inhibition Upregulates Connexin43 Expression in the Endothelium to Protect the Tight Junction Barrier in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Argonaute 2 Restores Erectile Function by Enhancing Angiogenesis and Reducing Reactive Oxygen Species Production in Streptozotocin (STZ)-Induced Type-1 Diabetic Mice.International journal of molecular sciences · 2023Article
- Anti-IL17A Halts the Onset of Diabetic Retinopathy in Type I and II Diabetic Mice.International journal of molecular sciences · 2023Article
- Choroidal circulation disturbance is an initial factor in outer retinal degeneration in rats under simulated weightlessness.Frontiers in physiology · 2023Article
- Connexin 43 across the Vasculature: Gap Junctions and Beyond.Journal of vascular research · 2023Review
- Ophthalmic artery changes in type 2 diabetes with and without acute coronary syndrome.Journal of translational medicine · 2022Article
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- Alterations in epidermal function in type 2 diabetes: Implications for the management of this disease.Journal of diabetes · 2022Review
- High Glucose Aggravates Retinal Endothelial Cell Dysfunction by Activating the RhoA/ROCK1/pMLC/Connexin43 Signaling Pathway.Investigative ophthalmology & visual science · 2022Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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Abstract
purposeTo investigate whether high glucose (HG)-induced downregulation of connexin 43 (Cx43), a gap junction protein, alters ZO-1 and occludin expression and cell monolayer permeability.
methodsRat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM) medium, high glucose (HG; 30 mM) medium, N medium transfected with Cx43 siRNA, or N medium transfected with scrambled siRNA. To determine Cx43, occludin, and ZO-1 protein expression, Western blot (WB) analysis and immunostaining were performed. Gap junction intercellular communication (GJIC) was determined using scrape load dye transfer (SLDT) assay. In parallel, cell monolayer permeability was assessed in the four groups of cells, and in cells transfected with Cx43 plasmid or dominant negative Cx43 plasmid.
resultsConnexin 43 protein expression was significantly reduced in cells grown in HG (67 ± 15% of control), and a significant reduction in Cx43 was achieved when cells grown in N medium were transfected with Cx43 siRNA (76 ± 12% of control), with concomitant decrease in GJIC activity. Cells grown in HG showed significant reduction in occludin (77 ± 9% of control) and ZO-1 (80 ± 11% of control) protein level compared with cells grown in N media. Importantly, cells transfected with Cx43 siRNA and grown in N medium showed significant downregulation in occludin (78 ± 8% of control) and ZO-1 (81 ± 6% of control) expression, and exhibited increased cell monolayer permeability. Furthermore, Cx43 upregulation protected cells against HG-induced excess cell monolayer permeability.
conclusionsOur findings indicate that HG-induced downregulation of Cx43 expression and GJIC may contribute to the breakdown of endothelial barrier tight junctions associated with diabetic retinopathy.
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