Gas6 regulates thrombin-induced expression of VCAM-1 through FoxO-1 in endothelial cells.

CONCLUSIONS: Thrombin induces VCAM-1 expression as well as FoxO-1 phosphorylation and nuclear exclusion in WT ECs only. Silencing FoxO-1 enhances VCAM-1 expression in both WT and Gas6(-/-) ECs. Inhibition of Akt or FoxO-1 phosphorylation prevents VCAM-1 expression in WT ECs. These data show that Gas6 induces FoxO-1 phosphorylation leading to de-repression of VCAM-1 expression. BM-MC/EC adhesion is increased by thrombin in WT ECs. BM-MC/EC adhesion is further increased when FoxO-1 is silenced but decreased when FoxO-1 phosphorylation is inhibited. These results demonstrate that the Gas6/FoxO-1 signaling axis plays an important role in VCAM-1 expression in the context of VTE by promoting BM-MC/EC adhesion. This article is protected by copyright. All rights reserved.
PMID: 26414399 [PubMed - as supplied by publisher]

Source: Thrombosis and Haemostasis - September 28, 2015 Category: Hematology Authors: Bertin FR, Lemarié CA, Robins RS, Blostein MD Tags: J Thromb Haemost Source Type: research