Down-Regulation of Notch Effects on Vascular Endothelial Growth Factor Pathway and Cell Proliferation of Bone Marrow Mesenchymal Stem Cells Co-Cultured with Endothelial Progenitor Cells

Previous studies have shown that Notch/DLL4 and vascular endothelial growth factor (VEGF) play critical regulatory roles in angiogenesis. Still, their function in vascular network construction of myocardial tissue engineered by bone marrow mesenchymal stem cells (BMSCs) need to be further discussed. The aim of this study is to down-regulate the expression of Notch gene by shRNA lentivirus vector in BMSCs which co-cultured with EPCs, and observe the influence on the subordinate protein and VEGF pathway, explore the change of BMSCs cell proliferation. BMSCs were infected with lentivirus vectors, then the stable transformants were selected and cocultured with EPCs, expression of target genes was identified by RT-qPCR and Western blot, cell proliferation was observed by CCK8. The data was analyzed by t-test in SPSS. The stable transformants were successfully constructed, expression of Notch gene and its subordinate protein NICD were significantly decreased interference by lentivirus. Expression of VEGF increased, and NICD decreased after interference. The level of cell proliferation in group shRNA was significantly higher than that in Blank group and NC group at 48 h (p < 0.05), and there was no interaction between time and grouping. The results indicate that Notch gene has a negative feedback effect on VEGF pathway, and downregulation of Notch gene promotes proliferation of BMSCs. There was an interaction between Notch and VEGF signal pathway in the regulation of engineered tissue angiogenesis.