Institute for Bioengineering of Catalonia (IBEC), 08028 Barcelona, Spain.
Biochem Biophys Res Commun. 2010 Feb 26;393(1):156-61. doi: 10.1016/j.bbrc.2010.01.109. Epub 2010 Feb 1.
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 Mg(2+) 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.
血管生成是一个由多种细胞类型和多种生化信号（如生长因子、转录因子、氧气和营养物质扩散等）调节的复杂过程。在本研究中，我们发现 Flk-1(+)CD34(+)祖细胞（骨髓中对血管生成具有重要作用的常驻细胞）对细胞外钙离子浓度的变化有反应，这是通过一种膜结合的、G 蛋白偶联受体来实现的，该受体对与钙敏感受体（CaSR）相关的钙离子敏感。钙离子能够诱导祖细胞在 Boyden 室实验中的迁移，并在 Matrigel 测定中诱导管状形成。添加抗 CaSR 抗体可完全阻断这种作用，而 CaSR 激动剂 Mg(2+)产生的反应与钙离子相似。对广泛的与血管生成相关的基因进行实时 RT-PCR 显示，内皮标记物和参与血管生成的信号通路的表达增加。这些结果表明，钙可能是骨髓祖细胞介导的血管生成反应的一种生理调节剂。
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