Nfat2 regulates cox-2 expression and modulates the integrin repertoire in endothelial cells at the crossroads of angiogenesis and inflammation.

NFAT2 REGULATES COX-2 EXPRESSION AND MODULATES THE INTEGRIN REPERTOIRE IN ENDOTHELIAL CELLS AT THE CROSSROADS OF ANGIOGENESIS AND INFLAMMATION.
Exp Cell Res. 2014 Mar 18;
Authors: Mena MP, Papiewska-Pajak I, Przygodzka P, Kozaczuk A, Boncela J, Cierniewski CS
Abstract
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 int...

Source: Experimental Cell Research - March 18, 2014 Category: Cytology Authors: Mena MP, Papiewska-Pajak I, Przygodzka P, Kozaczuk A, Boncela J, Cierniewski CS Tags: Exp Cell Res Source Type: research