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WIF1可防止Wnt5A介导的人血管内皮细胞中LIMK/CFL磷酸化及黏附连接破坏。

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

作者信息

Skaria Tom, Bachli Esther, Schoedon Gabriele

机构信息

Inflammation Research Unit, Division of Internal Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.

Department of Medicine, Uster Hospital, Brunnenstrasse 42, CH-8610 Uster, Switzerland.

出版信息

J Inflamm (Lond). 2017 May 19;14:10. doi: 10.1186/s12950-017-0157-4. eCollection 2017.

DOI:10.1186/s12950-017-0157-4
PMID:28529460
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5437570/
Abstract

BACKGROUND

Wnt5A 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.

FINDINGS

Here, 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.

CONCLUSION

We 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.

摘要

背景

Wnt5A由活化的巨噬细胞释放，在患有严重全身炎症的脓毒症患者中检测到其水平升高。然而，Wnt5A在血管内皮细胞（VEC）中的信号传导和功能作用仍不清楚。最近，我们发现Wnt5A通过与Ryk相互作用影响人VEC的屏障功能。Wnt5A/Ryk信号传导激活LIMK，通过磷酸化使肌动蛋白解聚因子CFL失活，促进肌动蛋白聚合并破坏内皮细胞黏附连接。

研究结果

在此，我们研究了Ryk特异性分泌的Wnt拮抗剂Wnt抑制因子（WIF）-1对Wnt5A介导的人VEC中LIMK/CFL激活/失活以及黏附连接破坏的拮抗作用。在人冠状动脉内皮细胞（HCAEC）中，Wnt5A处理增强了LIMK和CFL的磷酸化，而WIF1可显著阻止这种磷酸化。WIF1的存在抑制了Wnt5A介导的HCAEC中β-连环蛋白和VE-钙黏蛋白黏附连接的破坏，从而防止了由Wnt5A引起的屏障功能障碍。

结论

我们得出结论，WIF1或具有类似性质的分子可能是预防因Wnt5A介导的肌动蛋白细胞骨架重塑导致的血管渗漏的有效工具，这种血管渗漏发生在与全身炎症相关的疾病中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/a6a58721a41e/12950_2017_157_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/4a3ada77d57e/12950_2017_157_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/762d890b8fba/12950_2017_157_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/a6a58721a41e/12950_2017_157_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/4a3ada77d57e/12950_2017_157_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/762d890b8fba/12950_2017_157_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f5/5437570/a6a58721a41e/12950_2017_157_Fig3_HTML.jpg

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3
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Front Immunol. 2023 Jan 9;13:1090056. doi: 10.3389/fimmu.2022.1090056. eCollection 2022.
4
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Front Cardiovasc Med. 2022 Nov 11;9:997350. doi: 10.3389/fcvm.2022.997350. eCollection 2022.
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