Folic acid inhibits endothelial cell migration through inhibiting the RhoA activity mediated by activating the folic acid receptor/cSrc/p190RhoGAP-signaling pathway.

Folic acid inhibits endothelial cell migration through inhibiting the RhoA activity mediated by activating the folic acid receptor/cSrc/p190RhoGAP-signaling pathway. Biochem Pharmacol. 2012 Nov 23; Authors: Hou TC, Lin JJ, Wen HC, Chen LC, Hsu SP, Lee WS Abstract Previously, our in vivo studies demonstrated that folic acid (FA) could inhibit angiogenesis and in vitro studies showed that FA reduced vascular endothelial cell proliferation through activating the cSrc/ERK-2/NFκB/p53 pathway mediated by FA receptor (FR). Here, we further examined the effect of FA on endothelial cell migration. Our results showed that FA (10μM) inhibited the formation of lamellipodia, migration and capillary-like tube formation of human umbilical venous endothelial cells (HUVEC). These inhibition effects induced by FA treatment were not due to reduction of cell survival and cell adhesion on the collagen-coated plate. Treatment of HUVEC with FA (10μM) increased the activity of cSrc and p190RhoGAP and decreased the activity of RhoA. Over-expression of the constitutively active RhoA construct (RhoA V14) prevented the FA-induced inhibition of migration and capillary-like tube formation in HUVEC. However, these preventive effects were abolished by pretreatment of HUVEC with a ROCK inhibitor, Y27632. Pretreatment with a cSrc inhibitor, PP2, prevented the FA-induced activation of p190GAP, reduction of the RhoA activity and migration inhibition in HUVEC. Moreover, pre-tr...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research