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 7

Tight junction and venous cells are similarly affected by FGF signaling inhibition.

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Tight junction and venous cells are similarly affected by FGF signaling ...
(A) Immunostaining of quiescent endothelial monolayer (BAECs) transduced with Ad-GFP or Ad-FGFR1DN-GFP. Cells were stained for VE-cadherin (red) and ZO-1 (green). The Ad-FGFR1DN-GFP vector has a bidirectional promoter encoding both GFP and FGFR1DN as described above (GFP signal is shown in white). Arrows indicate reduced VE-cadherin and ZO-1 staining and gaps between endothelial cells. Scale bars: 20 μm. (B) Immunostaining of quiescent venous endothelial monolayer. HSVECs were transduced with Ad-GFP or Ad-FGFR1DN-GFP and stained for VE-cadherin (red) and p120-catenin (green) 24 hours later. Note loss of VE-cadherin and p120-catenin staining at cell-cell contacts and formation of intercellular gaps of FGFR1DN-GFP–transduced cells (white arrows). Scale bars: 20 μm.