Extracellular calcium modulates in vitro bone marrow-derived Flk-1+ CD34+ progenitor cell chemotaxis and differentiation through a calcium-sensing receptor
Extracellular calcium modulates in vitro bone marrow-derived Flk-1+ CD34+ progenitor cell chemotaxis and differentiation through a calcium-sensing receptor
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DOI：
10.1016/j.bbrc.2010.01.109
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发表时间：
2010-02-26
影响因子：
3.1
通讯作者：
Engel, E.
中科院分区：
文献类型：
--
作者：
Aguirre, A.;Gonzalez, A.;Engel, E.
血管生成是一个复杂的过程，受多种细胞类型和多种生化信号的调控，如生长因子、转录因子、氧和营养物质扩散等。在本研究中，我们发现Flk-1(+) CD34（+）祖细胞（在血管生成中起重要作用的骨髓常驻细胞）通过与钙敏感受体（CaSR）相关的膜结合的g蛋白偶联受体对钙离子敏感，从而响应细胞外钙浓度的变化。在Boyden室实验中，钙能诱导祖细胞迁移，在Matrigel实验中，钙能诱导小管形成。抗CaSR抗体的加入完全阻断了这一作用，而CaSR激动剂Mg2+产生了与钙类似的反应。实时RT-PCR检测多种血管生成相关基因显示内皮标志物和血管生成相关信号通路的表达增加。这些结果提示钙可能是骨髓祖细胞介导的血管生成反应的生理调节剂。(C) 2010爱思唯尔公司版权所有。
Angiogenesis is a complex process regulated by many cell types and a large variety of biochemical signals such as growth factors, transcription factors, oxygen and nutrient diffusion among others. In the present study, we found out that Flk-1(+) CD34(+) progenitor cells (bone marrow resident cells with an important role in angiogenesis) were responsive to changes in extracellular calcium concentration through a membrane bound, G-protein-coupled receptor sensitive to calcium ions related to the calcium-sensing receptor (CaSR). Calcium was able to induce progenitor cell migration in Boyden chamber experiments and tubulogenesis in Matrigel assays. Addition of anti-CaSR antibodies completely blocked the effect, while CaSR agonist Mg2+ produced a similar response to that of calcium. Real time RT-PCR for a wide array of angiogenesis-related genes showed increased expression of endothelial markers and signaling pathways involved in angiogenesis. These results suggest calcium could be a physiological modulator of the bone marrow progenitor cell-mediated angiogenic response. (C) 2010 Elsevier Inc. All rights reserved.