Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
J Cell Biochem. 2013 Aug;114(8):1843-51. doi: 10.1002/jcb.24526.
Caveolin-1 (CAV1) is the principal structural component of caveolae which functions as scaffolding protein for the integration of a variety of signaling pathways. In this study, we investigated the involvement of CAV1 in endothelial cell (EC) functions and show that siRNA-induced CAV1 silencing in the human EC line EA.hy926 induces distinctive morphological changes, such as a marked increase in cell size and formation of stress fibers. Design-based stereology was employed in this work to make unbiased quantification of morphometric properties such as volume, length, and surface of CAV1 silenced versus control cells. In addition, we showed that downregulation of CAV1 affects cell cycle progression at G1/S phase transition most likely by perturbation of AKT signaling. With the aim to assess the contribution of CAV1 to typical biological processes of EC, we report here that CAV1 targeting affects cell migration and matrix metalloproteinases (MMPs) activity, and reduces angiogenesis in response to VEGF, in vitro. Taken together our data suggest that the proper expression of CAV1 is important not only for maintaining the appropriate morphology and size of ECs but it might represent a prospective molecular target for studying key biological mechanisms such as senescence and tumorigenesis.
窖蛋白-1（CAV1）是质膜窖的主要结构成分，作为多种信号通路整合的支架蛋白发挥作用。在这项研究中，我们研究了 CAV1 在内皮细胞（EC）功能中的作用，并表明在人 EC 系 EA.hy926 中，siRNA 诱导的 CAV1 沉默诱导了独特的形态变化，例如细胞大小的显著增加和应激纤维的形成。本工作采用基于设计的体视学方法，对 CAV1 沉默与对照细胞的形态计量学特性（如体积、长度和表面）进行无偏定量。此外，我们表明 CAV1 的下调最有可能通过扰乱 AKT 信号转导而影响细胞周期在 G1/S 期转变中的进展。为了评估 CAV1 对 EC 典型生物学过程的贡献，我们在此报告 CAV1 靶向作用会影响细胞迁移和基质金属蛋白酶（MMPs）活性，并降低血管内皮生长因子（VEGF）刺激下的血管生成。综上所述，我们的数据表明，CAV1 的适当表达不仅对于维持 EC 的适当形态和大小很重要，而且它可能代表研究衰老和肿瘤发生等关键生物学机制的有前途的分子靶标。
