ArticleCellular and molecular life sciences : CMLS2016
Akt1 promotes stimuli-induced endothelial-barrier protection through FoxO-mediated tight-junction protein turnover.
Article in Cellular and molecular life sciences : CMLS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 50 citations in OpenAlex.
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- Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms.Cells · 2025Review
- Large-Scale Transcriptome Profiling and Network Pharmacology Analysis Reveal the Multi-Target Inhibitory Mechanism of Modified Guizhi Fuling Decoction in Prostate Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Specificity protein 1 initiates epithelial-mesenchymal transition of circulating tumor cells to inhibit metastasis in prostate cancer.Cancer cell international · 2025Article
- Claudin-17 Deficiency Drives Vascular Permeability and Inflammation Causing Lung Injury.International journal of molecular sciences · 2025Article
- NMN Supplementation Inhibits Endothelial Cell ROS-Mediated Src/Pi3k/Akt Signaling Pathway to Protect High-Altitude Blood-Retinal Barrier.Investigative ophthalmology & visual science · 2025Article
- Review
- Pharmacological Modulation of β-Catenin Preserves Endothelial Barrier Integrity and Mitigates Retinal Vascular Permeability and Inflammation.Journal of clinical medicine · 2023Article
- Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Claudin-17 Deficiency in Mice Results in Kidney Injury Due to Electrolyte Imbalance and Oxidative Stress.Cells · 2022Article
- Distinct Mechanisms of Human Retinal Endothelial Barrier Modulation In Vitro by Mediators of Diabetes and Uveitis.Life (Basel, Switzerland) · 2021Article
- Silencing Akt1 enhances the resistance of prostate cancer cells to starvation and inhibits starvation-induced lung metastasis through epithelial-mesenchymal transition in prostate cancer.Medical oncology (Northwood, London, England) · 2021Article
- Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/PPARγ signaling pathway.Annals of translational medicine · 2021Article
- Endothelial Extracellular Vesicles: From Keepers of Health to Messengers of Disease.International journal of molecular sciences · 2021Review
- Cisatracurium attenuates LPS-induced modulation of MMP3 and junctional protein expression in human microvascular endothelial cells.Bioscience trends · 2021Article
- Article
- Cell-cell junctions: structure and regulation in physiology and pathology.Tissue barriers · 2021Review
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
Vascular permeability regulated by the vascular endothelial growth factor (VEGF) through endothelial-barrier junctions is essential for inflammation. Mechanisms regulating vascular permeability remain elusive. Although 'Akt' and 'Src' have been implicated in the endothelial-barrier regulation, it is puzzling how both agents that protect and disrupt the endothelial-barrier activate these kinases to reciprocally regulate vascular permeability. To delineate the role of Akt1 in endothelial-barrier regulation, we created endothelial-specific, tamoxifen-inducible Akt1 knockout mice and stable ShRNA-mediated Akt1 knockdown in human microvascular endothelial cells. Akt1 loss leads to decreased basal and angiopoietin1-induced endothelial-barrier resistance, and enhanced VEGF-induced endothelial-barrier breakdown. Endothelial Akt1 deficiency resulted in enhanced VEGF-induced vascular leakage in mice ears, which was rescued upon re-expression with Adeno-myrAkt1. Furthermore, co-treatment with angiopoietin1 reversed VEGF-induced vascular leakage in an Akt1-dependent manner. Mechanistically, our study revealed that while VEGF-induced short-term vascular permeability is independent of Akt1, its recovery is reliant on Akt1 and FoxO-mediated claudin expression. Pharmacological inhibition of FoxO transcription factors rescued the defective endothelial barrier due to Akt1 deficiency. Here we provide novel insights on the endothelial-barrier protective role of VEGF in the long term and the importance of Akt1-FoxO signaling on tight-junction stabilization and prevention of vascular leakage through claudin expression.
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