Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB.
Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB.
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DOI：
10.1002/stem.2339
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Greene AS
中科院分区：
文献类型：
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作者：
Prisco AR;Hoffmann BR;Kaczorowski CC;McDermott-Roe C;Stodola TJ;Exner EC;Greene AS
在1997年发现内皮祖细胞（EPCs）后不久，进行了许多临床试验，使用EPCs作为基于细胞的疗法，目的是通过诱导新血管的生长（血管生成）来恢复受损的器官功能。结果令人失望，主要是因为EPC诱导血管生成的细胞和分子机制还不清楚。注射后，EPCs必须迁移到靶组织并在诱导血管生成之前植入。在这项研究中，研究了EPC迁移对肿瘤坏死因子α（TNFα）（一种促炎细胞因子）的反应，以检验缺血性疾病中观察到的器官损伤诱导对EPC归巢重要的炎症信号的假设。在这项研究中，使用共培养试验在体外模拟EPC迁移和掺入，其中在向血管样结构迁移时跟踪TNFα处理的EPC。结果发现，TNFα处理的EPCs增加迁移和纳入血管样结构。使用基因组学和蛋白质组学方法的组合，NF-κ B介导的CADM 1上调被确定为TNFα诱导的迁移机制。抑制NF-κ B或CADM 1可显著降低体外EPCs的迁移，提示TNFα信号在组织修复过程中EPC归巢中的作用。
Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with the goal of restoring damaged organ function by inducing growth of new blood vessels (angiogenesis). Results were disappointing, largely because the cellular and molecular mechanisms of EPC-induced angiogenesis were not clearly understood. Following injection, EPCs must migrate to the target tissue and engraft prior to induction of angiogenesis. In this study EPC migration was investigated in response to tumor necrosis factor α (TNFα), a pro-inflammatory cytokine, to test the hypothesis that organ damage observed in ischemic diseases induces an inflammatory signal that is important for EPC homing. In this study, EPC migration and incorporation were modeled in vitro using a co-culture assay where TNFα treated EPCs were tracked while migrating towards vessel-like structures. It was found that TNFα treatment of EPCs increased migration and incorporation into vessel-like structures. Using a combination of genomic and proteomic approaches, NF-kB mediated upregulation of CADM1 was identified as a mechanism of TNFα induced migration. Inhibition of NF-kB or CADM1 significantly decreased migration of EPCs in vitro suggesting a role for TNFα signaling in EPC homing during tissue repair.