文章摘要
盛祖龙,鞠成伟,鄢高亮,陈中璞,潘啸东,何砚如,瞿洋洋,姚玉宇,马根山.Fn14⁃PI3K⁃Akt介导TWEAK促人脐血内皮祖细胞血管生成研究[J].南京医科大学学报,2018,(5):571~576
Fn14⁃PI3K⁃Akt介导TWEAK促人脐血内皮祖细胞血管生成研究
Study on the angiogenesis of human umbilical cord blood endothelial progenitor cells mediated by Fn14⁃PI3K⁃Akt⁃induced TWEAK
投稿时间:2017-11-22  
DOI:10.7655/NYDXBNS20180501
中文关键词: 肿瘤坏死因子样弱凋亡因子  内皮祖细胞  血管新生  迁移  增殖
英文关键词: tumor necrosis factor⁃like attenuated apoptosis factor  human endothelial progenitor cells  angiogenesis  migration  proliferation
基金项目:国家自然科学基金资助项目(81400225);江苏省青年医学人才项目(QNRC2016815)
作者单位
盛祖龙 东南大学附属中大医院心血管内科江苏 南京 210009 
鞠成伟 东南大学附属中大医院心血管内科江苏 南京 210009 
鄢高亮 东南大学附属中大医院心血管内科江苏 南京 210009 
陈中璞 东南大学附属中大医院心血管内科江苏 南京 210009 
潘啸东 东南大学附属中大医院心血管内科江苏 南京 210009 
何砚如 东南大学附属中大医院心血管内科江苏 南京 210009 
瞿洋洋 东南大学附属中大医院心血管内科江苏 南京 210009 
姚玉宇 东南大学附属中大医院心血管内科江苏 南京 210009 
马根山 东南大学附属中大医院心血管内科江苏 南京 210009 
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中文摘要:
      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,hEPCs)增殖、迁移、血管形成能力的影响。方法:体外培养、分离和鉴定hEPCs,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:hEPCs体外培养实验表明,TWEAK可明显促进hEPCs的增殖和迁移,并能提升hEPCs的血管形成能力,但在TEWAK+Fn14 siRNA及TWEAK+LY组中hEPCs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hEPCs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。
英文摘要:
      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(hEPCs). Methods:hEPCs were isolated and identified in vitro. The hEPCs were treated with Fn14 siRNA and LY294002(LY),a specific inhibitor of PI3K. The cells were divided into the control group,the TWEAK treatment group,the TWEAK + Fn14 siRNA 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 hEPCs cultured in vitro showed that TWEAK significantly promoted the proliferation and migration of hEPCs and enhanced the vascularization ability of hEPCs. However,the proliferation,migration and angiogenesis ability of hEPCs in the TEWAK + Fn14 siRNA 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 siRNA group and the TWEAK + LY group was significantly lower than that in the TWEAK group. Conclusion:TWEAK can regulate the angiogenesis of hEPCs and its angiogenesis may be restricted by Fn14?PI3K?Akt signaling pathway.
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