Monomeric CXCL12 Outperforms Its Dimeric And Wild Type Variants In The Promotion Of Human Endothelial Progenitor Cells' Function

CXCL12 overexpression improves neurobehavioral recovery during post-ischemic stroke through multiple mechanisms including promoting endothelial progenitor cell function in animal models.It has been proposed that the monomer and dimer forms possess differential chemotactic and regulatory function.The aim of present study is to explore whether a monomeric or dimeric CXCL12 plays a different role in the endothelial progenitor cells proliferation,migration,and tube formation in vitro using a cultured endothelial progenitor cells.In this study,we transferred monomeric,dimeric and wild type CXCL12 gene into endothelial progenitor cells via lentiviral vectors.We investigated endothelial progenitor cells function following the interaction of CXCL12/ CXCR4 or CXCL12/CXCR7 and downstream signaling pathways.Our results showed that the monomeric CXCL12 transfected endothelial progenitor cells had enhanced ability in cell proliferation,migration,and tube formation compared to that in dimeric or wide type controls(p<0.05),which was associated with the VEGF overexpression.Both CXCR4 and CXCR7 were significantly overexpressed in the monomeric CXCL12 transfected endothelial progenitor cells compared to that in the dimeric or wide type controls(p<0.05).The function of migration,but not proliferation or tube formation,was significantly reduced in the monomeric CXCL12 transfected endothelial progenitor cells when the cells were pre-treated with either CXCR4 inhibitor AMD3100 or siCXCR7(p<0.05),suggesting this cell function was partially regulated by CXCL12/CXCR4 and CXCL12/CXCR7 signaling pathways.Our study demonstrated that monomeric CXCL12 was the fundamental form,which played the important role in endothelial progenitor cells proliferation,migration,and tube formation.