VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown

Argaw, Azeb Tadesse; Gurfein, Blake T.; Zhang, Yueting; Zameer, Andleeb; John, Gareth R.

doi:10.1073/pnas.0808698106

Cited by 565 publications

(501 citation statements)

References 41 publications

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“…However, the mechanism of the hyperpermeability induced by VEGF is still inclusive. It was reported that VEGF increased paracellular permeability (DeMaio et al 2004) and disrupted tight junction proteins claudin-5 (Argaw et al 2009). Meanwhile transcellular transport by caveolae was shown to mediate the VEGF-induced endothelial permeability, and cav-1 was colocated with KDR (Feng et al 1999;Zhao et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

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Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. b-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.

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Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

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“…During early embryogenesis, radial glia cells seem to be the source of VEGF needed for vascular development, although ECs have been described to promote cell-autonomous activation of the VEGF signaling (Lee et al 2007). Although VEGF is a factor mostly known to promote angiogenesis during development, in adulthood, VEGF decreases the stability of the BBB during inflammatory conditions (Argaw et al 2009(Argaw et al , 2012. Perivascular cells, including astrocytes, secrete angiopoietins (Ang1), which participate in the complex process of BBB differentiation by promoting angiogenesis and inducing a time-dependent decrease in endothelial permeability.…”

Section: Regulation Of the Bbb By Astrocytesmentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,533

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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“…However, VEGF also acts a BBB disaggregation signal via downregulation of endothelial tight junction components [137]. In specific pathological conditions such as CNS A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 25 inflammatory disorders, this pathway may exacerbate tissue damage by sustaining inflammation and leukocyte infiltration instead of supporting repair.…”

mentioning

confidence: 99%

“…3). VEGF is produced by reactive astrocytes after traumatic injury [136], inflammatory lesions, and hypoxic conditions ( [137] and references therein).…”

mentioning

confidence: 99%

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Buffo

Rolando

Ceruti

2010

Biochemical Pharmacology

288

260

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Running title: Beneficial and detrimental outcomes of astrogliosis after central nervous system injury. Abbreviations:Ado, adenosine; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate; AP1, activator protein1; AQP, acquaporin; BBB, blood-brain barrier; BDNF, brain-derived growth factor; bFGF, basic fibroblast growth factor; bHLH, basic helix loop helix; BMP, bone morphogenetic protein; CNS, central nervous system; CNTF, ciliary neurotrophic factor;COX-2, cyclooxigenase-2; CREB, cAMP response element binding; CSPGs, chondroitinsulphate proteoglycans; ERK, extracellular signal-regulated kinase; EGF, epidermal growth factor; Eph4A, ephrin 4A; Epo, erythropoietin; ET1, Endothelin 1; ET-R, endothelin receptor; GABA, gamma-aminobutyric acid; GDNF, glial cell-line derived neurotropic factor; GF, growth factor; GFAP, glial fibrillary acidic protein; GLAST, glutamate aspartate transporter; GLT1, glutamate transporter 1; GS, glutamine synthase; IFN , interferon-beta; IFNγ, interferon gamma; IGF1, insulin growth factor1; IL1β, interleukin 1 beta; IL2, interleukin 2; IL6, interleukin 6; IL10, interleukin 10; JAK, Janus protein tyrosine kinases; Lcn2, Lipocalin 2; MAPK, mitogen-activated protein kinase; MMP, matrix metalloprotease; mTOR, mammalian target of rapamycin; NFAT, nuclear factor of activated T cell; NFkB, nuclear factor kappa B; NGF, nerve growth factor; NT3, neurotrophin 3; p38MAPK, p38 mitogen-activated protein kinase; PTEN, phosphatase and tensin homolog; SOCS, suppressor of cytokine signaling; SOD, superoxide dismutase; STAT, signal transducers and activators of transcription; TGFα, transforming growth factor alpha;TGFβ, transforming growth factor beta; TNFα, tumor necrosis factor alpha; VCAM1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor. Page 4 of 63A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 4...

show abstract

VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown

Cited by 565 publications

References 41 publications

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

The Blood–Brain Barrier

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

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