Autocrine fibronectin directs matrix assembly and crosstalk between cell–matrix and cell–cell adhesion in vascular endothelial cells

Cseh, Botond; Fernandez-Sauze, Samantha; Grall, Dominique; Schaub, Sébastien; Doma, Eszter; Obberghen-Schilling, Ellen Van

doi:10.1242/jcs.073346

Cited by 64 publications

(83 citation statements)

References 78 publications

(77 reference statements)

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“…The requirement for polymerized versus protomeric fibronectin in the angiogenic process is not understood, but the finding suggests that the polymerizing fibronectin fibrils provide important angiogenic cues that are not found in protomeric fibronectin. This concept is supported by accumulating evidence indicating that fibronectin, its isoforms, its polymerization and its secondary structure all impact on neovascularization, indicative of an essential role for topographical organization of the fibronectin matrix in endothelial cell biology (Cseh et al, 2010;Le Saux et al, 2011;Mitsi et al, 2006;Uemura et al, 2006). In the present study, we show that anastellin, a homophilic binding peptide of fibronectin, drives conformational changes within the assembled fibronectin matrix that influence the endothelial microvessel cell response to angiogenic growth factors.…”

Section: Discussionsupporting

confidence: 67%

Conformational remodeling of the fibronectin matrix selectively regulates VEGF signaling

Ambesi

McKeown‐Longo

2014

Journal of Cell Science

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The fibronectin matrix plays a crucial role in the regulation of angiogenesis during development, tissue repair and pathogenesis. Previous work has identified a fibronectin-derived homophilic binding peptide, anastellin, as an effective inhibitor of angiogenesis; however, its mechanism of action is not well understood. In the present study, we demonstrate that anastellin selectively inhibits microvessel cell signaling in response to the VEGF 165 isoform, but not VEGF 121 , by preventing the assembly of the complex containing the VEGF receptor and neuropilin-1. Anastellin treatment resulted in the inactivation of a5b1 integrins but was not accompanied by a change in either adhesion complexes or adhesion-based signaling. Integrin inactivation was associated with a masking of the fibronectin synergy site within the extracellular matrix (ECM), indicating that a5b1 inactivation resulted from a decrease in available ligand. These data demonstrate that anastellin influences the microvessel cell response to growth factors by controlling the repertoire of ligated integrins and point to anastellin as an effective regulator of fibronectin matrix organization. These studies further suggest that homophilic fibronectin binding peptides might have novel applications in the field of tissue regeneration as tools to regulate neovascularization.

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Section: Discussionsupporting

confidence: 67%

Conformational remodeling of the fibronectin matrix selectively regulates VEGF signaling

Ambesi

McKeown‐Longo

2014

Journal of Cell Science

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“…However, recent in vivo studies suggest that in addition to paracrine functions (Yoshino et al, 2014), Fn1 could also signal in a cell-autonomous manner (Cseh et al, 2010;Liu et al, 2010;Serres et al, 2014;Stenzel et al, 2011). By using genetic and cell biological approaches, the studies reported in this paper are the first to demonstrate the requisite, cell-autonomous role of Fn1 in the regulation of cardiovascular development.…”

Section: Role Of Fn1 and Integrin α5 In Nc Development And Cardiovascmentioning

confidence: 81%

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Wang

Astrof

2015

Development

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The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We show that NC Fn1 signals in an NC cell-autonomous manner through integrin α5β1 expressed by the NC, leading to activation of Notch and differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling.

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“…37 In the absence of subendothelial FN matrix, endothelial cells are thought to undergo a switch from ␣ 5 ␤ 1 to ␣ v ␤ 3 integrin-based adhesion, associated with a disruption of adherens junctions. 38 In turn, ␣ v ␤ 3 engagement promotes angiogenesis, in part via interaction with VEGF receptor 2. 39 Thus, FN cleavage by extracellular calpains would promote angiogenesis by both generating proangiogenic fragments and limiting FN adhesive functions.…”

Section: Discussionmentioning

confidence: 99%

Calpains Contribute to Vascular Repair in Rapidly Progressive Form of Glomerulonephritis: Potential Role of Their Externalization

Letavernier

Zafrani

Nassar

et al. 2012

ATVB

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Objective-Calpains, calcium-activated proteases, mediate the angiogenic signals of vascular endothelial growth factor.However, their involvement in vascular repair has not been investigated and the underlying mechanisms remain to be fully elucidated. Methods and Results-A rapidly progressive form of glomerulonephritis in wild type and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor, was studied. Calpastatin transgene expression prevented the repair of peritubular capillaries and the recovery of renal function, limiting mouse survival. In vitro analysis detected a significant reduction of both intracellular and extracellular calpain activities in transgene expressing cells, whereas Western blotting revealed that proangiogenic factors vascular endothelial growth factor and norepinephrine increased calpain exteriorization. In vitro, extracellular calpains increased endothelial cell proliferation, migration and capillary tube formation. In vivo, delivery of nonpermeable extracellular calpastatin was sufficient to blunt angiogenesis and vascular repair. Endothelial cell response to extracellular calpains was associated with fibronectin cleavage, generating fibronectin fragments with proangiogenic capacity. In vivo, fibronectin cleavage was limited in the kidney of calpastatin transgenic mice with nephritis. Conclusion-This

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Autocrine fibronectin directs matrix assembly and crosstalk between cell–matrix and cell–cell adhesion in vascular endothelial cells

Cited by 64 publications

References 78 publications

Conformational remodeling of the fibronectin matrix selectively regulates VEGF signaling

Conformational remodeling of the fibronectin matrix selectively regulates VEGF signaling

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Calpains Contribute to Vascular Repair in Rapidly Progressive Form of Glomerulonephritis: Potential Role of Their Externalization

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