Caldesmon-dependent switching between capillary endothelial cell growth and apoptosis through modulation of cell shape and contractility.
Caldesmon-dependent switching between capillary endothelial cell growth and apoptosis through modulation of cell shape and contractility.
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DOI：
10.1023/a:1025821517679
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发表时间：
2003-01-01
期刊：
影响因子：
9.8
通讯作者：
Ingber, Donald E.
中科院分区：
文献类型：
--
作者：
Numaguchi, Yasushi;Huang, Sui;Ingber, Donald E.
钙调素（CaD），肌动球蛋白丝装置的蛋白质成分，调节细胞的形状和细胞骨架结构时，过表达。当毛细血管内皮细胞感染的腺病毒载体编码GFP-CaD Tet-Off控制下，进行性抑制收缩，肌动蛋白应力纤维的损失，解体的焦点粘连，和细胞回缩的结果。这伴随着细胞形状（变圆）依赖性的细胞凋亡增加和伴随的细胞周期进程抑制。细胞生长也受到抑制，在低表达细胞中，细胞张力受到抑制的细胞形状，细胞骨架结构，或局灶性粘连的显着变化独立。因此，细胞骨架结构和收缩性的变化似乎是毛细血管细胞形状的细胞外基质依赖性变化影响血管生成过程中生长和凋亡的机制的核心，因此细胞骨架可能代表抗血管生成治疗的潜在靶点。
Caldesmon (CaD), a protein component of the actomyosin filament apparatus, modulates cell shape and cytoskeletal structure when overexpressed. When capillary endothelial cells were infected with an adenoviral vector encoding GFP-CaD under Tet-Off control, progressive inhibition of contractility, loss of actin stress fibers, disassembly of focal adhesions, and cell retraction resulted. This was accompanied by a cell shape (rounding)-dependent increase in apoptosis and concomitant inhibition of cell cycle progression. Cell growth also was inhibited in low expressor cells in which cell tension was suppressed independently of significant changes in cell shape, cytoskeletal structure, or focal adhesions. Thus, changes in both cytoskeletal structure and contractility appear to be central to the mechanism by which extracellular matrix-dependent changes in capillary cell shape influence growth and apoptosis during angiogenesis, and hence the cytoskeleton may represent a potential target for anti-angiogenesis therapy.