Scherberich A, Campos-Toimil M, Rondé P, Takeda K, Beretz A
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, France.
J Cell Sci. 2000 Feb;113 ( Pt 4):653-62. doi: 10.1242/jcs.113.4.653.
Migration of vascular smooth muscle cells (VSMC) is a key event in the formation of neointima during atherosclerosis. Fura-2 loaded VSMCs were used to investigate calcium homeostasis during cell migration. Multiple spontaneous transient increases in cytosolic free calcium Ca(2+)were observed in single human VSMCs migrating on type I collagen. Such Ca(2+)transients were dependent on the presence of serum or PDGF-BB. Removal of serum, or loading cells with BAPTA, abolished the transients and decreased cell migration speed. The transients were not affected by disruption of cell polarization by dihydrocytochalasin B. Adhesion was used to investigate the specific role of cell-substrate interactions in the generation of transients. Transients are seen in VSMCs adhering either on collagen or on poly-L-lysine, suggesting that generation of transients is not strictly dependent on integrins. Buffering Ca(2+) with BAPTA led to accumulation of (beta)1 integrins at the cellular tail, and to increased release of integrin on the extracellular matrix. These results demonstrate a role for Ca(2+) transients in the rapid, serum-dependent migration of VSMCs. These Ca(2+)transients are present in migrating VSMCs only when two simultaneous events occur: (1) substrate independent spreading and (2) stimulation of cells by serum components such as PDGF-BB.
血管平滑肌细胞（VSMC）的迁移是动脉粥样硬化过程中新内膜形成的关键事件。用Fura-2负载的VSMC来研究细胞迁移过程中的钙稳态。在I型胶原上迁移的单个原代人VSMC中观察到多次胞质游离钙[Ca(2+)]i的自发性瞬时升高。这种[Ca(2+)]i瞬变依赖于血清或血小板衍生生长因子BB（PDGF-BB）的存在。去除血清或用BAPTA加载细胞可消除瞬变并降低细胞迁移速度。二氢细胞松弛素B破坏细胞极化对瞬变没有影响。通过黏附来研究细胞-底物相互作用在瞬变产生中的具体作用。在黏附于胶原或聚-L-赖氨酸的VSMC中都能看到瞬变，这表明瞬变的产生并不严格依赖于整合素。用BAPTA缓冲[Ca(2+)]i会导致β1整合素在细胞尾部积累，并增加整合素在细胞外基质上的释放。这些结果证明了[Ca(2+)]i瞬变在VSMC快速、血清依赖性迁移中的作用。只有当两个同时发生的事件出现时，迁移的VSMC中才会出现这些[Ca(2+)]i瞬变：（1）不依赖底物的铺展和（2）血清成分如PDGF-BB对细胞的刺激。
