DFO Enhances the Targeting of CD34-Positive Cells and Improves Neovascularization
DFO Enhances the Targeting of CD34-Positive Cells and Improves Neovascularization
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DOI：
10.3727/096368914x685753
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发表时间：
2015-11
影响因子：
3.3
通讯作者：
Zijing Du;T. Zan;Xiaolu Huang;Lingling Sheng;Haizhou Li;Hua Li;Qingfeng Li
中科院分区：
文献类型：
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作者：
Zijing Du;T. Zan;Xiaolu Huang;Lingling Sheng;Haizhou Li;Hua Li;Qingfeng Li
去铁胺（DFO）是一种铁螯合剂，通过抑制HIF-1α降解和上调血管生成因子来模拟缺氧。在本实验中，我们阐明了DFO对cd34阳性细胞迁移和新生血管的影响。cd34阳性细胞在含有DFO或抑制剂的培养基中培养，进行体外小管形成和因子表达。将裸鼠随机分为5组，每组12只：对照组、CD34组、CD34- dfo组、CD34- dfo - amd组（AMD3100， CXCR4抑制剂）和CD34- dfo - ly组（LY294002， PI3K抑制剂）。采用激光散斑成像（LSI）和生物发光成像（BLI）评估肢体灌注和体内成像。术后第14天检测毛细血管密度，并探讨相关机制。在体外，DFO显著增加了cd34阳性细胞的成管和血管生成因子的表达，这些因子被PI3K抑制剂LY294002阻断。DFO增强了血流量、缺血后肢功能和VEGF水平。此外，p-eNOS和p-Akt在缺血后升高。BLI显示，DFO增加了靶向缺血部位的cd34阳性细胞的数量。免疫组织荧光显示，DFO治疗组缺血后肢毛细血管密度明显高于其他组。然而，LY294002减少了所有这些影响。DFO通过PI3K/Akt信号转导通路增强了缺血后肢中cd34阳性细胞的靶向性，改善了新生血管的形成。
Desferoxamine (DFO), an iron chelator, mimicked hypoxia by inhibiting HIF-1α degradation and upregulated angiogenic factors. In this experiment, we elucidated the effect of DFO on CD34-positive cell migration and neovascularization. CD34-positive cells were cultured in media with DFO or an inhibitor and subjected to in vitro tubule formation and the expression of factors. Nude mice were randomly divided into five groups of 12: control, CD34, CD34-DFO, CD34-DFO-AMD (AMD3100, CXCR4 inhibitor), and CD34-DFO-LY (LY294002, the PI3K inhibitor) groups. Limb perfusion and in vivo imaging was evaluated by laser speckle imaging (LSI) and bioluminescence imaging (BLI). Capillary density was examined 14 days after surgery, and the relevant mechanism was also explored. In vitro, DFO significantly increased the tube formation and expression of angiogenic factors in CD34-positive cells, which were blocked by the PI3K inhibitor, LY294002. DFO enhanced blood flow, the function of the ischemic hindlimb, and the levels of VEGF. Further, p-eNOS and p-Akt increased in response to the ischemia. BLI showed that DFO increased the number of CD34-positive cells targeted to the ischemic sites. Immunohistofluorescence revealed that the capillary density in the ischemic hindlimb was significantly higher in the DFO treatment group compared with the other groups. However, all of these effects were diminished by LY294002. DFO treatment enhanced CD34-positive cell targeting and improved neovascularization via the PI3K/Akt signal transduction pathway in an ischemic hindlimb.