The FGF system has a key role in regulating vascular integrity
Masahiro Murakami, … , Radu V. Stan, Michael Simons
Masahiro Murakami, … , Radu V. Stan, Michael Simons
Published September 5, 2008
Citation Information: J Clin Invest. 2008;118(10):3355-3366. https://doi.org/10.1172/JCI35298.
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The FGF system has a key role in regulating vascular integrity

Abstract

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF signaling using these approaches resulted in dissociation of the VE-cadherin/p120-catenin complex and disassembly of adherens and tight junctions, which progressed to loss of endothelial cells, severe impairment of the endothelial barrier function, and finally, disintegration of the vasculature. Thus, FGF signaling plays a key role in the maintenance of vascular integrity.

Authors

Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Peter Carmeliet, Radu V. Stan, Michael Simons

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Figure 6

Junction proteins are absent from cell-cell contacts in cells lacking FGF signaling.

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Junction proteins are absent from cell-cell contacts in cells lacking FG...
(A) Immunostaining of quiescent and fully confluent endothelial monolayer. BAECs were transduced with Ad-GFP or Ad-FGFR1DN-GFP using low MOI (10 and 25, respectively) to limit the number of transduced cells and minimize virus-mediated toxicity. Cells were stained for VE-cadherin (red) and β-catenin (green) 24 hours later. The Ad-FGFR1DN-GFP vector has a bidirectional promoter encoding both GFP and FGFR1DN, thus marking transduced cells with GFP (shown in white). Note the loss of VE-cadherin and β-catenin staining at cell-cell contacts of FGFR1DN-GFP–transduced cells. Arrow points to the gap between neighboring FGFR1DN-GFP–transduced cells. Scale bars: 20 μm. (B) Immunostaining of quiescent endothelial monolayer (BAECs) transduced with Ad-Null or Ad-sFGFR1IIIc. Cells were stained for VE-cadherin (red), p120-catenin (green), and DAPI (blue). sFGFR was secreted in the medium; the effect is not limited to the transduced cells. Arrows indicate gaps between endothelial cells. Scale bars: 20 μm.