Gene expression profile of adult human bone marrow-derived mesenchymal stem cells stimulated by the chemokine CXCL7
Gene expression profile of adult human bone marrow-derived mesenchymal stem cells stimulated by the chemokine CXCL7
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DOI：
10.1016/j.biocel.2008.07.011
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发表时间：
2009-03-01
影响因子：
4
通讯作者：
Kaps, Christian
中科院分区：
文献类型：
--
作者：
Kalwitz, Gregor;Endres, Michaela;Kaps, Christian
各种趋化因子已被证明可以招募人骨髓间充质干细胞（MSC），并可能成为基于趋化因子的组织再生方法的潜在候选者。本研究的目的是确定趋化因子CXCL 7是否刺激人骨髓来源的MSC的迁移，并在广泛的分子水平上分析CXCL 7对MSC募集的影响。趋化性测定证明CXCL 7的高关闭显著招募MSC。使用寡核苷酸微阵列的基因表达谱显示，与CXCL 7处理的MSC差异表达的基因与细胞迁移，细胞粘附和细胞外基质重塑。通路分析显示CXCL 7诱导结合白细胞介素（IL）受体A和B、CXCR 1和CXCR 2的所有趋化因子的表达，以及ILG信号转导子（gp 130）及其配体ILG和白血病抑制因子（LIF）。通过实时聚合酶链反应验证了CXCL 7对MSC中差异表达的趋化因子CXCL 1 -3、CXCL 5和CXCLG以及LIF和gp 130的诱导。细胞培养上清液的免疫测定证实了在用CXCL 7处理后MSC中白细胞介素G和8的水平升高。趋化性试验表明，白细胞介素G没有招募MSC。总之，CXCL 7在体外显著刺激人MSC的迁移。途径分析表明，CXCL 7对人MSC的募集是通过诱导白细胞介素8受体的配体来支持的，协同激活各自的信号传导途径。(C)2008爱思唯尔有限公司保留所有权利。
A variety of chemokines has been shown to recruit human bone marrow-derived mesenchymal stem cells (MSC) and may be potential candidates for chemokine-based tissue regeneration approaches. The aim of our study was to determine whether the chemokine CXCL7 stimulates migration of human bone marrow-derived MSC and to analyze the effect of CXCL7 on the recruitment of MSC oil the broad molecular level. Chemotaxis assays documented that high closes of CXCL7 significantly recruited MSC. Gene expression profiling using oligonucleotide microarrays showed that MSC treated with CXCL7 differentially expressed genes related to cell migration, cell adhesion and extracellular matrix remodeling. Pathway analysis showed that CXCL7 induced the expression of all chemokines binding the interleukin (IL) receptors A and B, CXCR1 and CXCR2, as well as the ILG signal transducer (gp130) and its ligands ILG and leukemia inhibitory factor (LIF). Induction of differentially expressed chemokines CXCL1-3, CXCL5, and CXCLG as well as LIF and gp130 in MSC by CXCL7 was verified by real-time polymerase chain reaction. Immunoassay of cell culture supernatants confirmed elevated levels of the interleukins G and 8 in MSC upon treatment with CXCL7. Chemotaxis assays showed that interleukin G did not recruit MSC. In conclusion, CXCL7 significantly stimulates the migration of human MSC in vitro. Pathway analysis suggests that recruitment of human MSC by CXCL7 is supported by the induction of ligands of the interleukin 8 receptors, synergistically activating the respective signaling pathways. (C) 2008 Elsevier Ltd. All rights reserved.