Objective: To investigate the mechanism(s) that prostaglandin E1 (PGE1) promotes human umbilical vein endothelial cell (HUVEC)proliferation and migration.
Methods: Western blot, enzyme linked immunosorbent assay, cell proliferation and cell migration tests, and tube formation were used for analyzing the roles and mechanisms of PGE1 on HUVEC; Western blot was used for analyzing the effects of PGE1 on the expression of vascular endothelial growth factor (VEGF) in rat aortic vascular smooth muscle cells (VSMC).
Results: PGE1 significantly increased VEGF expression of HUVEC in time and a dose dependent manner with concomitantly increased HUVEC proliferation; treatment of HUVEC with Bevacizumab apparently suppressed PGE1-stimulated VEGF expression, which led to decreased tube formation, reduced cell proliferation and migration by 41% and 38%, respectively, compared with PGE1 treatment alone; PGE1 time-dependently induced both phosphorylation of ERK and p38 in HUVEC, whereas ERK inhibitor, PD98059, or p38 inhibitor, SB203580, blocked PGE1-induced VEGF expression of HUVEC, resulting in dramatically suppression of HUVEC proliferation and migration compared with PGE1 treatment alone (60% and 55% by PD98059, 62% and 51% by SB203580, respectively); in addition, cAMP-dependent protein kinase A inhibitor, H89 or Rp-cAMP blocked PGE1-induced VEGF expression in VSMC.
Conclusion: PGE1 promotion of proliferation, migration and tube formation of HUVEC via VEGF further provides a novel theoretical support in efficacy of PGE1 treatment of critical limb ischemia and other related diseases.