Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells
Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells
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DOI：
10.1007/s10456-011-9242-0
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发表时间：
2012-03-01
期刊：
影响因子：
9.8
通讯作者：
Maier, Jeanette A. M.
中科院分区：
文献类型：
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作者：
Baldoli, Erika;Maier, Jeanette A. M.
越来越多的证据表明，镁可能在控制血管生成中发挥作用。由于微血管内皮细胞在这个过程中的主角，我们研究了这些细胞的行为培养在低细胞外镁或沉默其转运蛋白瞬时受体电位Melastatin（TRPM）7，细胞镁稳态必不可少的。特别是，我们专注于血管生成过程中的一些关键步骤，即增殖，迁移，蛋白酶的生产和组织的三维结构。沉默TRPM 7模拟低细胞外镁对人微血管内皮细胞（HMEC）的影响。事实上，虽然没有观察到对金属蛋白酶的产生和对基质胶上的三维组织的影响，但镁缺乏和TRPM 7的沉默都损害细胞迁移并通过将细胞阻滞在细胞周期的G 0/G1和G2/M期来抑制生长。由于低细胞外镁显着降低TRPM 7在HMEC中，我们认为TRPM 7下调可能介导低镁诱导的细胞生长和迁移抑制。来自脐静脉的人内皮细胞的生长受到低镁的抑制，并且在TRPM 7沉默后生长受到刺激。HMEC沉默TRPM 7中ERK磷酸化的损伤部分地负责这两种细胞类型的不同增殖行为。我们还将我们的研究扩展到内皮集落形成细胞，并发现它们对细胞外镁浓度的波动敏感，而它们的增殖速率不受TRPM 7沉默的调节。我们的研究结果指出镁和TRPM 7作为微血管内皮细胞的血管生成表型的调节剂。
Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells.