Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis

Abstract

Our data provide the first evidence of visfatin-induced endothelial VEGF and MMP production and activity. Further, we show for the first time the involvement of the MAPK and PI3K/Akt signalling pathways in mediating these actions, as well as endothelial cell proliferation. Collectively, our findings provide novel insights into visfatin-induced endothelial angiogenesis.

Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis

“…A few previous studies have evaluated the role of visfatin in endothelial cells and have suggested that visfatin may function to improve endothelial cell function and support postnatal angiogenesis (1,8). Although the mechanism(s) of these effects remain unclear, they may involve activation of MAP kinase ERK-dependent pathways, upregulation of vascular endothelial growth factor, and/or stimulation of PI 3-kinase/ Akt pathways.…”

NAMPT (visfatin) in the chicken testis: influence of sexual maturation on cellular localization, plasma levels and gene and protein expression

“…Moreover, male Sirt1 K/K knockout mice had increased proportion of mature sperm with elevated DNA damage, while a microarray analysis of SIRT1-deficient testis revealed dysregulated expression of 85 genes that are involved in spermatogenesis and protein sumoylation (Coussens et al 2008). In addition to increasing NAD production, NAMPT has been found to increase expression of vascular endothelial growth factor (VEGFA) and VEGFA receptor-2 in vascular endothelial cells through activation of the MAP kinase (MAPK1) and phosphatidylinositol-3-kinase/ AKT1 pathways (Adya et al 2008). VEGF increases NAMPT expression in the chicken testis vascular endothelial cell proliferation in the testis (Rudolfsson et al 2004) and can therefore affect testicular vascularization.…”

Suppression of leukocyte infiltration and cartilage degradation by selective inhibition of pre-B cell colony-enhancing factor/visfatin/nicotinamide phosphoribosyltransferase: Apo866-mediated therapy in human fibroblasts and murine collagen-induced arthrit

“…Several groups have shown that PBEF interacts with the insulin receptor (8-10); however, this notion remains controversial (11,12), and it may be that PBEF signals through an alternative signaling route. It is also unlikely that this signaling effect is attributable to the endotoxin that may be present in PBEF preparations, since coincubation with polymixin B shows no abrogation of PBEF signaling (6,10,13).In vitro activation of signaling pathways by PBEF has been shown to regulate the expression of metalloproteinases, chemokines, and cytokines (6,7,(9)(10)(11)(12), but the in vivo contribution of this mediator of arthritis progression remains unclear. The recently developed small molecule inhibitor APO866 has been shown to act as a competitive inhibitor of PBEF/NAMPT activity by inhibiting binding of its natural substrate, nicotinamide (14,15).…”

“…processes via activation of transcriptional events through NF-B, phosphatidylinositol 3-kinase, and MAP kinase (6)(7)(8). Several groups have shown that PBEF interacts with the insulin receptor (8)(9)(10); however, this notion remains controversial (11,12), and it may be that PBEF signals through an alternative signaling route.…”

“…In vitro activation of signaling pathways by PBEF has been shown to regulate the expression of metalloproteinases, chemokines, and cytokines (6,7,(9)(10)(11)(12), but the in vivo contribution of this mediator of arthritis progression remains unclear. The recently developed small molecule inhibitor APO866 has been shown to act as a competitive inhibitor of PBEF/NAMPT activity by inhibiting binding of its natural substrate, nicotinamide (14,15).…”