Effect of hypoxia on gene expression of bone marrow-derived mesenchymal stem cells and mononuclear cells
Effect of hypoxia on gene expression of bone marrow-derived mesenchymal stem cells and mononuclear cells
复制标题
DOI：
10.1634/stemcells.2006-0347
复制
发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Nagaya, Noritoshi
中科院分区：
文献类型：
--
作者：
Ohnishi, Shunsuke;Yasuda, Takeshi;Nagaya, Noritoshi
MSC具有自我更新和多向分化潜能，包括向内皮细胞和血管平滑肌细胞分化。尽管骨髓来源的单核细胞（MNC）已被应用于缺血组织中的治疗性血管生成，但有关MNC与其MSC亚群之间的分子基础以及它们对缺血条件的反应的比较的信息很少。因此，我们使用包含31，099个基因的微阵列研究了常氧和缺氧条件下大鼠骨髓MSC和MNC之间的基因表达谱。在常氧条件下，MSC和MNC中分别有2，232（7.2%）和2，193（7.1%）个基因优先表达超过3倍，MSC表达了许多参与发育、形态发生、细胞粘附和增殖的基因，而MNC中高表达的各种基因参与炎症反应和趋化性。低氧条件下，MSC和MNC中分别有135个（0.44%）和49个（0.16%）基因表达上调（> 3倍），其中大量基因参与糖酵解和代谢。针对分泌蛋白编码基因，缺氧条件下MSC中上调的基因包括几种参与细胞增殖和存活的分子，如血管内皮生长因子-D、胎盘生长因子、前B细胞集落增强因子1、肝素结合表皮生长因子样生长因子和基质金属蛋白酶-9，而在低氧条件下，MNC中上调的基因包括促炎细胞因子，如趋化因子（CXC基序）配体2和白细胞介素-1 α。我们的研究结果可能提供信息的差异分子机制调节缺血条件下的MSC和MNC的属性。
MSC have self-renewal and multilineage differentiation potential, including differentiation into endothelial cells and vascular smooth muscle cells. Although bone marrow-derived mononuclear cells ( MNC) have been applied for therapeutic angiogenesis in ischemic tissue, little information is available regarding comparison of the molecular foundation between MNC and their MSC subpopulation, as well as their response to ischemic conditions. Thus, we investigated the gene expression profiles between MSC and MNC of rat bone marrow under normoxia and hypoxia using a microarray containing 31,099 genes. In normoxia, 2,232 (7.2%) and 2,193 genes (7.1%) were preferentially expressed more than threefold in MSC and MNC, respectively, and MSC expressed a number of genes involved in development, morphogenesis, cell adhesion, and proliferation, whereas various genes highly expressed in MNC were involved in inflammatory response and chemotaxis. Under hypoxia, 135 (0.44%) and 49 (0.16%) genes were upregulated (> threefold) in MSC and MNC, respectively, and a large number of those upregulated genes were involved in glycolysis and metabolism. Focusing on genes encoding secretory proteins, the upregulated genes in MSC under hypoxia included several molecules involved in cell proliferation and survival, such as vascular endothelial growth factor-D, placenta growth factor, pre-B-cell colony-enhancing factor 1, heparin-binding epidermal growth factor-like growth factor, and matrix metalloproteinase-9, whereas the upregulated genes in MNC under hypoxia included proinflammatory cytokines such as chemokine (CXC motif) ligand 2 and interleukin-1 alpha. Our results may provide information on the differential molecular mechanisms regulating the properties of MSC and MNC under ischemic conditions.