Proteomic Profiling of Secreted Proteins for the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells

Proteomic Profiling of Secreted Proteins for the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells
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DOI:
10.3727/096368912x657288
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发表时间:
2013-01-01
影响因子:
3.3
通讯作者:
Salama, Abdulgabar
Salama, Abdulgabar
中科院分区:
医学4区
文献类型:
--
作者:
Bal, Guerkan;Kamhieh-Milz, Julian;Salama, Abdulgabar

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人脐静脉内皮细胞(HUVECs)分泌的多种因子对造血干细胞和祖细胞(HSPCs)的增殖和分化有重要影响。这些因素在很大程度上仍然未知。在这里,我们报告了最全面的蛋白质组分析的HUVEC分泌组,并确定了827种不同的分泌蛋白。在所有条件下发现231种蛋白质,而仅在IL-1 β、IL-3和IL-6刺激后的促炎条件下鉴定出369种蛋白质。仅在IL-1 β和IL-3条件下鉴别出13种蛋白质,包括补体因子B(CF B),可能代表HSPC增殖因子。生物信息学和基因本体注释的结合表明了补体系统及其激活的作用。此外,发现CFb在转录上强烈上调。在干细胞扩增试验中加入补体成分5 b-9(C5 b-9)单克隆抗体能够显著降低其增殖。这项研究表明,在促炎条件下,内皮细胞和HSPC之间存在补体介导的串扰。
Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the most comprehensive proteomic profiling of the HUVEC secretome and identified 827 different secreted proteins. Two hundred and thirty-one proteins were found in all conditions, whereas 369 proteins were identified only under proinflammatory conditions following IL-1 beta, IL-3, and IL-6 stimulation. Thirteen proteins including complement factor b (CFb) were identified only under IL-1 beta and IL-3 conditions and may potentially represent HSPC proliferation factors. The combination of bioinformatics and gene ontology annotations indicates the role of the complement system and its activation. Furthermore, CFb was found to be transcriptionally strongly upregulated. Addition of complement component 5b-9 (C5b-9) monoclonal antibody to the stem cell expansion assay was capable of significantly reducing their proliferation. This study suggests a complement-mediated cross-talk between endothelial cells and HSPCs under proinflammatory conditions.