Hemangiopoietin promotes endothelial cell proliferation through PI-3K/Akt pathway

Abstract

Hemangiopoietin (HAPO) is a novel human growth factor acting on the primitive cells of both hematopoietic and endothelial cell lineages. Our previous study has shown that HAPO exerts a proliferative effect on endothelial cells. However, the mechanism of this action remains unclear. Thus, we studied the signal transduction pathway whereby HAPO promotes cell proliferation in human umbilical vein endothelial cells (HUVECs). In this study, recombinant human HAPO (rhHAPO) stimulated the proliferation of HUVECs in a dose-dependent manner. The transient phosphorylation of Akt occurred after addition of rhHAPO to HUVECs. LY294002, a specific inhibitor of PI-3K, significantly inhibited Akt phosphorylation and completely abrogated HAPO-stimulated proliferation of HUVECs. rhHAPO enhanced the expression of cyclin D1, where as LY294002 inhibited the up-regulation of cyclin D1. Moreover, rhHAPO is able to selectively enhance the mitogenic activity of VEGF for vascular endothelial cells. Overall, these findings demonstrate that HAPO induces endothelial cell proliferation through the PI-3K/Akt pathway.