Essential role for calcium waves in migration of human vascular smooth muscle cells
Essential role for calcium waves in migration of human vascular smooth muscle cells
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DOI：
10.1152/ajpheart.00355.2010
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发表时间：
2011-08-01
影响因子：
4.8
通讯作者：
Sims, Stephen M.
中科院分区：
文献类型：
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作者：
Espinosa-Tanguma, Ricardo;O'Neil, Caroline;Sims, Stephen M.
Espinosa-Tanguma R，O 'Neil C，Chrones T，Pickering JG，西姆斯SM.钙波在人血管平滑肌细胞迁移中的重要作用。美国生理学杂志心脏循环生理学301：H315-H323，2011年。首次发表于2011年5月13日; doi：10.1152/ajpheart.00355.2010.-血管平滑肌细胞（SMC）迁移的特征在于前缘的板状伪足的延伸、板状伪足与基底的附着以及细胞后部（尾足）的释放，所有这些都使得能够向前运动。然而，关于细胞内胞质Ca 2+浓度（[Ca 2 +]（i））在协调这些不同的活动迁移SMC的作用知之甚少。我们的研究目的是确定是否区域变化的Ca 2+编排迁移周期在人血管平滑肌细胞。我们使用数字荧光显微镜对fura-2加载的人平滑肌细胞进行了Ca 2+成像。我们发现，能动的平滑肌细胞表现出典型的钙离子波，从后面的极化细胞向前缘扫。在非极化的静止细胞中，Ca 2+波不太明显，尽管用激动剂血小板衍生生长因子-BB或组胺急性刺激这些SMC可引起[Ca 2 +]的短暂升高（i）。为了研究Ca 2+波在迁移周期中的作用，我们用Ca 2+螯合剂BAPTA加载细胞，其消除了Ca 2+波并显著减少了收缩，支持Ca 2+在收缩起始中的因果作用。然而，在BAPTA负载的细胞中，片足运动仍然明显。当用肌浆网Ca 2 +-ATP酶抑制剂thapsigargin或用肌醇1，4，5-三磷酸盐受体阻断剂2-氨基乙氧基-二苯基硼酸酯或xestospongin C处理细胞内钙库释放的钙时，钙振荡的发生率降低，暗示钙库在波的产生中。我们的结论是，钙波是必不可少的人血管平滑肌细胞的迁移，并可以编码细胞极性。
Espinosa-Tanguma R, O'Neil C, Chrones T, Pickering JG, Sims SM. Essential role for calcium waves in migration of human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 301: H315-H323, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00355.2010.-Vascular smooth muscle cell (SMC) migration is characterized by extension of the lamellipodia at the leading edge, lamellipodial attachment to substrate, and release of the rear (uropod) of the cell, all of which enable forward movement. However, little is known regarding the role of intracellular cytosolic Ca2+ concentration ([Ca2+](i)) in coordinating these distinct activities of migrating SMCs. The objective of our study was to determine whether regional changes of Ca2+ orchestrate the migratory cycle in human vascular SMCs. We carried out Ca2+ imaging using digital fluorescence microscopy of fura-2 loaded human smooth muscle cells. We found that motile SMCs exhibited Ca2+ waves that characteristically swept from the rear of polarized cells toward the leading edge. Ca2+ waves were less evident in nonpolarized, stationary cells, although acute stimulation of these SMCs with the agonists platelet-derived growth factor-BB or histamine could elicit transient rise of [Ca2+](i). To investigate a role for Ca2+ waves in the migratory cycle, we loaded cells with the Ca2+ chelator BAPTA, which abolished Ca2+ waves and significantly reduced retraction, supporting a causal role for Ca2+ in initiation of retraction. However, lamellipod motility was still evident in BAPTA-loaded cells. The incidence of Ca2+ oscillations was reduced when Ca2+ release from intracellular stores was disrupted with the sarcoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin or by treatment with the inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxy-diphenyl borate or xestospongin C, implicating Ca2+ stores in generation of waves. We conclude that Ca2+ waves are essential for migration of human vascular SMCs and can encode cell polarity.