Regulation of Vascular Endothelial Growth Factor Expression by Extra Domain B Segment of Fibronectin in Endothelial Cells

Chen, Shali; Chakrabarti, Rana; Keats, Emily C.; Chen, Megan; Chakrabarti, Subrata; Khan, Zia A.

doi:10.1167/iovs.12-9766

Cited by 18 publications

(16 citation statements)

References 58 publications

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“…A connection between a2b1 integrin function and VEGF-A induction was first reported by Chen et al, 9 who showed in human umbilical vein endothelial cells that inhibitory antibodies to a2b1 integrin blocked hyperglycemia-induced VEGF-A expression. Our observation of the same phenomena in a distinct cell type (Müller cells as opposed to endothelial cells), in a different species (mouse versus human), with a different stimulus (hypoxia versus hyperglycemia) raises the possibility of a broadly applicable role for the a2b1 integrin in regulating VEGF-A expression.…”

Section: Discussionmentioning

confidence: 66%

“…[6][7][8] In pathological conditions, overproduction of growth factors, most prominently VEGF, stimulates retinal NV. Chen et al 9 suggest that a2b1 integrin may have an important role in regulating VEGF production in endothelial cells under conditions of hyperglycemia. In the retina, endothelial cells and many other cell types, including astrocytes, retinal pigment epithelial cells, and ganglion cells, contribute to VEGF overproduction; however, animal models have identified Müller cells as the predominant source of VEGF during retinal NV.…”

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confidence: 99%

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Mitigation of Oxygen-Induced Retinopathy in α2β1 Integrin-Deficient Mice

Madamanchi

Capozzi

Geng

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The a2b1 integrin plays an important but complex role in angiogenesis and vasculopathies. Published GWAS studies established a correlation between genetic polymorphisms of the a2b1 integrin gene and incidence of diabetic retinopathy. Recent studies indicated that a2-null mice demonstrate superior vascularization in both the wound and diabetic microenvironments. The goal of this study was to determine whether the vasculoprotective effects of a2-integrin deficiency extended to the retina, using the oxygeninduced retinopathy (OIR) model for retinopathy of prematurity (ROP).METHODS. In the OIR model, wild-type (WT) and a2-null mice were exposed to 75% oxygen for 5 days (postnatal day [P] 7 to P12) and subsequently returned to room air for 6 days (P12-P18). Retinas were collected at postnatal day 7, day 13, and day 18 and examined via hematoxylin and eosin and Lectin staining. Retinas were analyzed for retinal vascular area, neovascularization, VEGF expression, and Müller cell activation. Primary Müller cell cultures from WT and a2-null mice were isolated and analyzed for hypoxia-induced VEGF-A expression.RESULTS. In the retina, the a2b1 integrin was minimally expressed in endothelial cells and strongly expressed in activated Müller cells. Isolated a2-null primary Müller cells demonstrated decreased hypoxia-induced VEGF-A expression. In the OIR model, a2-null mice displayed reduced hyperoxia-induced vaso-attenuation, reduced pathological retinal neovascularization, and decreased VEGF expression as compared to WT counterparts.CONCLUSIONS. Our data suggest that the a2b1 integrin contributes to the pathogenesis of retinopathy. We describe a newly identified role for a2b1 integrin in mediating hypoxiainduced Müller cell VEGF-A production.

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Section: Discussionmentioning

confidence: 66%

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confidence: 99%

Mitigation of Oxygen-Induced Retinopathy in α2β1 Integrin-Deficient Mice

Madamanchi

Capozzi

Geng

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…It might be possible that, in combination with DCN, its conformation and function is also changed [96][97][98]. It has been shown that conformational remodeling of the FN matrix selectively regulates VEGF signaling [121]. VEGF in turn regulates VEGFR2 expression [113].…”

Section: Discussionmentioning

confidence: 99%

Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

Daum

Visser

Wild

et al. 2020

Cells

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Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.

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“…Previous studies also identified VEGF-binding sites on fibronectin (Wijelath et al. , 2002, 2006), and fibronectin was shown to regulate VEGF secretion via integrins (Chen et al. , 2012).…”

Section: Discussionmentioning

confidence: 99%

Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane

Guzmán-Hernández

Potter

Égervári

et al. 2014

MBoC

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Regulation of Vascular Endothelial Growth Factor Expression by Extra Domain B Segment of Fibronectin in Endothelial Cells

Abstract: These findings showed that high levels of glucose in diabetes increased VEGF expression in ECs through ED-B FN and β1 integrin interaction. These results provide novel mechanistic basis of increased VEGF expression in diabetes.

Cited by 18 publications

References 58 publications

Mitigation of Oxygen-Induced Retinopathy in α2β1 Integrin-Deficient Mice

Mitigation of Oxygen-Induced Retinopathy in α2β1 Integrin-Deficient Mice

Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane

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