WIF1 prevents Wnt5A mediated LIMK/CFL phosphorylation and adherens junction disruption in human vascular endothelial cells

Journal of Inflammation

Short Report

Esther Bachli¹  Tom Skaria²  Gabriele Schoedon² 

[1] Department of Medicine, Uster Hospital, Brunnenstrasse 42, CH-8610, Uster, Switzerland;Inflammation Research Unit, Division of Internal Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091, Zürich, Switzerland;

关键词: Inflammation;    Endothelial permeability;    Wnt5A;    WIF1;    Ryk;    Cytoskeleton remodeling;   

DOI  :  10.1186/s12950-017-0157-4

 received in 2017-01-19, accepted in 2017-05-12,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundWnt5A is released by activated macrophages and elevated levels have been detected in sepsis patients with severe systemic inflammation. However, the signalling and functional effects of Wnt5A in the vascular endothelial cells (VEC) remained unclear. Recently, we showed that Wnt5A affects barrier function in human VEC through Ryk interaction. Wnt5A/Ryk signalling activates LIMK to inactivate the actin depolymerisation factor CFL by phosphorylation, promotes actin polymerisation and disrupts endothelial adherens junctions.FindingsHere, we investigate the antagonistic effect of the Ryk specific secreted Wnt antagonist Wnt inhibitory factor (WIF)-1 on Wnt5A-mediated activation/inactivation of LIMK/CFL, and adherens junction disruption in human VEC. In human coronary artery endothelial cells (HCAEC), treatment with Wnt5A enhanced the phosphorylation of LIMK and CFL that was significantly prevented by WIF1. The presence of WIF1 suppressed Wnt5A-mediated disruption of β-catenin and VE-cadherin adherens junctions in HCAEC, thereby preventing barrier dysfunction caused by Wnt5A.ConclusionWe conclude that WIF1 or molecules with similar properties could be potent tools for the prevention of vascular leakage due to Wnt5A-mediated actin cytoskeleton remodeling in diseases associated with systemic inflammation.

【 授权许可】

CC BY   
© The Author(s). 2017