整合素integrinβ4调控VEGF诱导的骨髓间充质r干细胞向内皮细胞分化

摘要

血管内皮生长因子(vascular endothelial growth factor,VEGF)可以诱导间充质干细胞(mesenchymal stem cells,MSCs)向内皮细胞(endothelial cells,ECs)分化,但分化机制尚不清楚.本研究鉴定了整合素integrinβ4在VEGF诱导的MSCs向ECs分化过程中表达明显上调,同时利用亚硫酸氢盐测序法(EZ DNA Methylation)分析了5-aza-dc和VEGF处理MSCs后的integrinβ4启动子CpG岛发生部分的去甲基化.在分化过程中持续加入integrinβ4的功能阻断性抗体,可显著降低内皮分化标志基因KDR(endothelial gene kinase insert domain containing receptor,KDR)、Flt-1的表达.以上结果表明,integrinβ4可调控VEGF诱导的MSCs向ECs分化.%Vascular endothelial growth factor(VEGF)can induce mesenchymal stem cells(MSCs)to undergo endothelial cells(ECs)differentiation,but the mechanism of differentiation remains unclear.This study identified that the expression of integrin β4 was upregulated in endothelial differentiation from MSCs to ECs induced by VEGF.At the same time,The CpG-rich promoter regions of integrin β4 were all demethylated by EZ DNA Methylation in MSCs treated with 5-aza-dc and VEGF.When the function-blocking antibodies of integrin β4 were added in the differentiation continuously,the expression of endothelial differentiation marker genes,the endothelial gene kinase insert domain containing receptor(KDR) and Flt-1 were induced.These results suggest that integrin β4 can regulate ECs from MSCs induced by VEGF.