Hypoxic Preconditioning Enhances Biological Function of Endothelial Progenitor Cells via Notch-Jagged1 Signaling Pathway

缺氧预处理通过 Notch-Jagged1 信号通路增强内皮祖细胞的生物学功能

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作者:Qian Wang, LiHua Liu, YuanYuan Li, Jinfeng Wang, Yun Liu, QinQin Wu, Bin Wang, Benming Qi, BenLing Qi

Abstract

BACKGROUND Hypoxic preconditioning may be a key influence on functions of endothelial progenitor cells (EPCs). MATERIAL AND METHODS To investigate the role and mechanism of the Notch-Jagged1 pathway on endothelial progenitor cells in hypoxic preconditioning, endothelial progenitor cells were randomly allocated into 5 groups: 1 Normoxic control group; 2 Hypoxic blank group; 3 Hypoxic+25 μM DAPT group; 4 Hypoxic+50 μM DAPT group; 5 Hypoxic+100 μM DAPT group. After reoxygenation, protein and mRNA levels of Jagged1 were measured by Western blot and quantitative RT-PCR. The MTT test was used to assess proliferation. ELISA was used to measure NO and VEGF secretion. RESULTS Hypoxic preconditioning treatment significantly upregulated both protein and mRNA levels of Jagged1 in endothelial progenitor cells. It also enhanced proliferation ability and elevated secretion of NO and VEGF. Furthermore, after blocking the Notch pathway by using DAPT, Jagged1 expression and EP proliferation, migration, and secretion of NO and VEGF were decreased in a dose-dependent manner. CONCLUSIONS Our results suggest the Notch-Jagged1 pathway enhances EPCs proliferation and secretion ability during hypoxic preconditioning.

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