Caveolin-1 expression enhances endothelial capillary tubule formation
Caveolin-1 expression enhances endothelial capillary tubule formation
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DOI：
10.1074/jbc.m110354200
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发表时间：
2002-03-22
影响因子：
4.8
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
--
作者：
Liu, J;Wang, XB;Lisanti, MP
Caveolin-1的表达水平与NIH 3T3细胞的致癌转化、人类癌细胞的增殖以及脂肪细胞和肌肉细胞的分化密切相关。然而，caveolin-1在内皮细胞增殖和分化中的作用仍不清楚。在这里，我们发现刺激内皮细胞增殖的血管生成生长因子会导致 eaveolin-1 表达急剧减少。此外，我们使用体外基质胶测定系统，利用人微血管内皮细胞（HMEC-1）研究了caveolin-1在毛细血管样小管形成（即内皮细胞分化）中的潜在作用。我们发现，当内皮细胞分化时，内源性 eaveolin-1 表达水平以时间依赖性方式增加，并且在毛细血管样小管形成之前，caveolin-1 表达达到最高水平。有趣的是，通过腺病毒基因传递系统，caveolin-1 的过度表达明显加速了内皮细胞分化/小管形成，并导致毛细血管样管状结构数量急剧增加 3 倍。相反，通过反义腺病毒方法下调caveolin-1表达，使形成的毛细血管样小管的数量减少>10倍。与 Caveolin-1 与关键信号分子相互作用的独特功能一致，将 Caveolin-1 支架结构域递送到活内皮细胞的细胞质中也足以增强毛细血管样小管的形成。总之，这些结果清楚地表明，caveolin-1和caveolin-1支架结构域在内皮细胞分化的调节中发挥着重要的积极作用，而内皮细胞分化是血管生成过程中的先决步骤。
The level of caveolin-1 expression closely correlates with the oncogenic transformation of NIH 3T3 cells, the proliferation of human cancer cells, and the differentiation of adipocytes and muscle cells. However, the role of caveolin-1 in endothelial cell proliferation and differentiation remains unknown. Here, we have shown that angiogenic growth factors that stimulate endothelial cell proliferation lead to dramatic reductions in eaveolin-1 expression. In addition, using an in vitro Matrigel assay system, we studied the potential role of caveolin-1 in capillary-like tubule formation (i.e. endothelial cell differentiation) using human microvascular endothelial cells (HMEC-1). We showed that the level of endogenous eaveolin-1 expression increased in a time-dependent manner when endothelial cells underwent differentiation and that the maximum level of caveolin-1 expression occurred just prior to the formation of capillary like tubules. Interestingly, overexpression of caveolin-1, via an adenoviral gene delivery system, clearly accelerated endothelial cell differentiation/tubule formation and led to a dramatic similar to3-fold increase in the number of capillary-like tubular structures. Conversely, down-regulation of caveolin-1 expression, via an antisense adenoviral approach, reduced the number of capillary-like tubules formed by >10-fold. Consistent with the unique function of caveolin-1 in interacting with key signaling molecules, delivery of the caveolin-1 scaffolding domain into the cytoplasm of living endothelial cells was also sufficient to enhance capillary-like tubule formation. Taken together, these results clearly demonstrate that caveolin-1 and the caveolin-1 scaffolding domain play an important positive role in the regulation of endothelial cell differentiation, a prerequisite step in the process of angiogenesis.