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目的:探讨Fn14-PI3K-Akt信号通路介导的肿瘤坏死因子样弱凋亡因子(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)对人脐血来源的内皮祖细胞(human endothelial progenitor cells,h EPCs)增殖、迁移、血管形成能力的影响.方法:体外培养、分离和鉴定h EPCs,以其受体成纤维细胞生长因子14 siRNA(Fn14 siRNA)及PI3K特异性抑制剂LY294002(LY)作干预处理.细胞分为对照组、TWEAK干预组、TWEAK+Fn14 siRNA阻断组和TWEAK+LY阻断组.分别采用CCK-8法检测细胞增殖能力,Transwell小室检测细胞迁移能力,Matrigel小管形成试验评价细胞血管生成能力,Western blot法测定细胞裂解液中p-Akt和T-Akt的表达.结果:h EPCs体外培养实验表明,TWEAK可明显促进h EPCs的增殖和迁移,并能提升h EPCs的血管形成能力,但在TEWAK+Fn14 siRNA及TWEAK+LY组中h EPCs的增殖、迁移及血管形成能力显著降低.且TWEAK组p-Akt表达较对照组显著增加,而TWEAK+Fn14siRNA组、TWEAK+LY组p-Akt表达较TWEAK组显著降低.结论:TWEAK具有调控h EPCs促血管新生的作用,其促血管新生的作用可能受到Fn14-PI3K-Akt信号通路的限制.“,”Objective:To investigate the effects of tumor necrosis factor-like attenuated apoptosis factor (TWEAK) mediated by Fn14-PI3K-Akt signaling pathway on the proliferation, migration and angiogenesis of human umbilical cord blood derived human endothelial progenitor cells (h EPCs). Methods:h EPCs were isolated and identified in vitro. The h EPCs were treated with Fn14 si RNA and LY294002 (LY), a specific inhibitor of PI3 K. The cells were divided into the control group, the TWEAK treatment group, the TWEAK + Fn14 si RNA blocking group and the TWEAK + LY treatment group. Cell proliferation was measured by CCK-8 assay, cell migration assay was performed in Transwell chamber, and angiogenesis ability was evaluated by Matrigel tubule formation assay. The expressions of p-Akt and T-Akt in cell lysate were measured by Western blot. Results:The h EPCs cultured in vitro showed that TWEAK significantly promoted the proliferation and migration of h EPCs and enhanced the vascularization ability of h EPCs. However, the proliferation, migration and angiogenesis ability of h EPCs in the TEWAK + Fn14 si RNA group and the TWEAK + LY groups were significantly decreased. The expression of p-Akt in the TWEAK group was significantly higher than that in the control group, while the expression of p-Akt in the TWEAK + Fn14 si RNA group and the TWEAK + LY group was significantly lower than that in the TWEAK group. Conclusion:TWEAK can regulate the angiogenesis of h EPCs and its angiogenesis may be restricted by Fn14-PI3 K-Akt signaling pathway.