Modulating Endothelial Barrier Function by Targeting Vimentin Phosphorylation. Issue 10 (October 2014)

• Record Type: Journal Article
• Authors: Liu, Tiegang; Ghamloush, Maher M.; Aldawood, Ali; Warburton, Rod; Toksoz, Deniz; Hill, Nicholas S.; Tang, Dale D.; Kayyali, Usamah S.
• Is Part Of: Journal of cellular physiology. Volume 229:Issue 10(2014:Oct.)
• Page Start: 1484
• Page End: 1493
• Publication Date: 2014-10
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24590
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jcp24590-sec-0001" sec-type="section"> <p>Vimentin is a major intermediate filament protein in vascular endothelial cells which might be involved in their function as a barrier tissue. It is proposed to dynamically maintain integrity of the endothelium as a tightly regulated permeability barrier that is subjected to a variety of shear and contractile forces. The results described in this report demonstrate that vimentin plays that role through mechanisms that are dependent on its phosphorylation state. Withaferin A (WFA), a vimentin targeting drug is shown to disrupt endothelial barrier function through its effects on vimentin filament distribution and physical properties. These effects are related to WFA's ability to increase vimentin phosphorylation. Through overexpressing a non‐phosphorylatable vimentin mutant we can block the effects of WFA on vimentin distribution and barrier permeability. The barrier augmentation effect appears to extend to endothelial cells that do not express detectable mutant vimentin which might suggest transmissible effects across cells. Blocking vimentin phosphorylation also protects the endothelial barrier against LPS endotoxin, implicating it as a target for drug development against pulmonary edema and acute respiratory distress syndrome (ARDS). J. Cell. Physiol. 229: 1484–1493, 2014. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>