Article ID Journal Published Year Pages File Type
2130308 Experimental Cell Research 2014 13 Pages PDF
Abstract

•Integrin profile induced by VEGF-A is distinct from that brought on by TNF-α.•Upregulation of integrin subunits by VEGF-A is sensitive to NFAT-inhibitors.•NFAT2 controls VEGF-induced COX-2 expression.•NFAT2 modulates the integrin repertoire induced by VEGF-A.

The mechanisms controlling the switch between the pro-angiogenic and pro-inflammatory states of endothelial cells are still poorly understood. In this paper, we show that: (a) COX-2 expression induced by VEGF-A is NFAT2-dependent; and (b) the integrin profile in endothelial cells induced by the pro-angiogenic VEGF-A is distinct from that brought on by the inflammatory cytokine TNF-α. Two groups of integrin subunits specifically upregulated over time by both cytokines were identified using RT-PCR and Western Immunoblotting. The first group included α4, α5, α6, and β5 subunits that were upregulated by VEGF-A; the second group consisted of αV and β3 induced by TNF-α. Both cytokines significantly enhanced the expression of β1 and modulated α2 mRNA. In contrast to TNF-α, VEGF-A induction of integrin subunits depended on the activation of the calcineurin/NFAT pathway. Both calcineurin inhibitors (cyclosporineA and 11R-VIVIT) and downregulation of NFAT2 with specific siRNA decreased induction of integrin subunits. This process of induction could be increased by upregulation of NFAT2 by pBJ5-NFAT2 transfection. This suggests that NFAT2 mediates VEGF-induced upregulation of integrin subunit synthesis by providing a constant supply of newly synthesized “refreshed” mature integrin receptors, particularly α2β1, α5β1, α4β1, α6β1 and αVβ5, which are involved at different stages of angiogenesis.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
Authors
, , , , , ,