ArticleInvestigative ophthalmology & visual science2017
Compound 49b Regulates ZO-1 and Occludin Levels in Human Retinal Endothelial Cells and in Mouse Retinal Vasculature.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
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- Müller Glia Co-Regulate Barrier Permeability with Endothelial Cells in an Vitro Model of Hyperglycemia.International journal of molecular sciences · 2024Article
- Semaphorin 7a regulates inflammatory mediators and permeability in retinal endothelial cells.Microvascular research · 2023Article
- VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer's mice.Brain : a journal of neurology · 2022Article
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
- VEGF Paradoxically Reduces Cerebral Blood Flow in Alzheimer's Disease Mice.Neuroscience insights · 2022Article
- Disruption of tight junctions contributes to hyposalivation of salivary glands in a mouse model of type 2 diabetes.Journal of anatomy · 2020Article
- Review: Role of cAMP signaling in diabetic retinopathy.Molecular vision · 2020Review
- Scutellarein alleviates the dysfunction of inner blood-retinal-barrier initiated by hyperglycemia-stimulated microglia cells.International journal of ophthalmology · 2020Article
- Epac1 protects the retina against ischemia/reperfusion-induced neuronal and vascular damage.PloS one · 2018Article
- The role of small GTPases and EPAC-Rap signaling in the regulation of the blood-brain and blood-retinal barriers.Tissue barriers · 2017Review
- Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1Mediators of inflammation · 2017Article
- Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System.Journal of diabetes research · 2017Article
- Qingchang Wenzhong Decoction Attenuates DSS-Induced Colitis in Rats by Reducing Inflammation and Improving Intestinal Barrier Function via Upregulating the MSP/RON Signalling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: To investigate whether Epac1 is key to Compound 49b's regulation of zonula occluden 1 (ZO-1) and occludin levels in human retinal endothelial cells (REC) and in an Epac1 vascular-specific conditional knockout mouse retina. Methods: Primary REC were grown in normal (5 mM) or high glucose (25 mM). Some cells were treated with a novel β-adrenergic receptor agonist, Compound 49b. Additional dishes were treated with Epac1 siRNA or Compound 49b + Epac1 siRNA. Protein levels of ZO-1, occludin, VEGF, and protein kinase C zeta (PKCz) were measured by Western blotting. Cell permeability was measured in REC grown in normal or high glucose and treated with Compound 49b, a specific Epac 1 agonist (8-CPT-2'-O-Me-cAMP), or VEGF. Epac1 floxed and cdh5-Cre mice were bred to generate Epac1 knockout mice in vascular endothelial cells. Immunofluorescence was done on retinal flatmounts from the floxed and Cre-Lox mice for occludin and ZO-1. Western blotting was also done for both proteins in whole retinal lysates from the mice. Results: High glucose significantly reduced ZO-1 and occludin protein levels, which was associated with reduced cell adhesion. Compound 49b increased endothelial cell barrier protein levels through active Epac1. Knockout of Epac1 in vascular endothelial cells substantially reduced ZO-1 and occludin staining in retinal flatmounts, as well as protein levels. Conclusions: Compound 49b increased ZO-1 and occludin protein levels, likely leading to decreased permeability.
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