GLP-1 regulates proliferation, differentiation and apoptosis of endothelial progenitor cells isolated from human umbilical cord blood by targeting the SDF-1/CXCR4 signaling pathway / 天津医药

ABSTRACT

Objective To investigate the molecular regulatory mechanism of glucagon like peptide 1 (GLP-1) on proliferation, differentiation and apoptosis of human umbilical cord blood endothelial progenitor cells (EPCs). Methods EPCs were isolated from the umbilical cord blood of healthy pregnant women and cultured in 6-hole cell plate at 2×105 density in vitro, transfected with empty vector plasmid (control group), pcDNA3-GLP-1 plasmid (GLP-1 group), pcDNA3-GLP-1plasmid+AMD3100 (GLP-1+AMD3100 group) and simple AMD3100 (AMD3100 group). The pcDNA3-GLP-1 was transfected into EPCs. The 25μmol/L AMD3100 was used to block the SDF-1/CXCR4 signal pathway of EPCs for 1 h. The cell proliferation was determined by MTT method. The mRNA expressions of differentiation and apoptosis related genes PPARγ, C/EBPα and Caspase-3 were investigated by RT-PCR, and Caspase-3 activity was determined by Caspase-3 activity assay kit. Results Compared to control group, AMD3100 inhibitor showed no effects on cell proliferation, differentiation and apoptosis, while over-expression of GLP-1 in EPCs obviously promoted cell proliferation, and differentiation related genes PPARγand C/EBPαmRNA expression, but down-regulated mRNA expression and the activity of Caspase-3 significantly (P＜0.05), indicating that GLP-1 increased proliferation and differentiation of EPCs while decreased cell apoptosis. When the SDF-1/CXCR4 signaling pathway was blocked by AMD3100, over-expression of GLP-1 induced promotion of cell proliferation, and the differentiation was decreased significantly and the apoptosis was significantly increased (P＜0.05). Conclusion These data confirm that GLP-1 might promote EPCs proliferation and differentiation, and inhibit cell apoptosis through the regulation of the SDF-1/CXCR4 signaling pathway.