Thy-1-Induced Migration Inhibition in Vascular Endothelial Cells through Reducing the RhoA Activity

Abstract

Our previous study indicated that Thy-1, which is expressed on blood vessel endothelium in settings of pathological and a specific of physiological, but not during embryonic, angiogenesis, may be used as a marker for angiogenesis. However, the function of Thy-1 during angiogenesis is still not clear. Here, we demonstrate that knock-down of the endogenous Thy-1 expression by Thy-1 siRNA transfection promoted the migration of human umbilical vein endothelial cells (HUVEC). In contrast, treatment with interleukin-1β (IL-1β) or phorbol-12-myristate-13-acetate (PMA) increased the level of Thy-1 protein and reduced the migration of HUVEC. These effects were abolished by pre-transfection of HUVEC with Thy-1 siRNA to knock-down the expression of Thy-1. Moreover, over-expression of Thy-1 by transfection of HUVEC with Thy-1 pcDNA3.1 decreased the activity of RhoA and Rac-1 and inhibited the adhesion, migration and capillary-like tube formation of these cells. These effects were prevented by co-transfection of the cell with constitutively active RhoA construct (RhoA V14). On the other hand, pre-treatment with a ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor, Y27632, abolished the RhoA V14-induced prevention effect on the Thy-1-induced inhibition of endothelial cell migration and tube formation. Taken together, these results indicate that suppression of the RhoA-mediated pathway might participate in the Thy-1-induced migration inhibition in HUVEC. In the present study, we uncover a completely novel role of Thy-1 in endothelial cell behaviors.

PMA inhibits endothelial cell migration through activating the PKC-δ/Syk/NF-κB-mediated up-regulation of Thy-1

“…We previously demonstrated that Thy-1 can serve as a marker for adult angiogenesis 13 . We also showed that expression of Thy-1 can inhibit endothelial cell migration, but did not affect endothelial cell proliferation 14 . In the present study, we used PMA as a Thy-1 inducer to further investigate how the Thy-1 expression is regulated.…”

“…Previously, we demonstrated that Thy-1 can serve as a novel marker of adult, but not embryonic, angiogenesis 13 . We also demonstrated that overexpression of Thy-1 inhibited vascular endothelial cell migration and capillary-like tube formation through reducing the RhoA activity 14 . However, the molecular mechanism underlying Thy-1 up-regulation in vascular endothelial cells is still not clear.…”

“…Previous in vitro studies showed that phorbol-12-myristate-13-acetate (PMA) can up-regulate Thy-1 expression in human dermal microvascular endothelial cells (HDMECs) 15 . We also showed that PMA can reduce the endothelial migration, and this effect was abolished by knock-down of Thy-1 expression using siRNA technique 14 . Accordingly, we used PMA as an inducer of Thy-1 expression to investigate the regulation of Thy-1 expression in vascular endothelial cells and the effect of PMA on angiogenesis.…”

Células-tronco mesenquimais: isolamento e caracterização de populações derivadas de alvéolo dental humano e identificação e caracterização de populações de polpas dentais de camundongos

“…Acredita-se que o CD90 está envolvido em vários processos celulares como proliferação, diferenciação, apoptose, adesão, e migração (Wen et al, 2013). O CD90 é expresso durante os processos de angiogênese fisiológica e patológica, mas não durante o desenvolvimento embrionário (Lee et al, 1998).…”

“…O CD90 é expresso durante os processos de angiogênese fisiológica e patológica, mas não durante o desenvolvimento embrionário (Lee et al, 1998). O aumento da expressão de CD90 em células endoteliais em cultivo inibe a adesão, migração e formação de tubos capilares, enquanto o bloqueio da expressão endógena de CD90 ocasiona a migração destas células (Wen et al, 2013).…”