Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, 8330025, Chile.
Escuela de Medicina, Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, 8370007, Chile.
Biol Direct. 2023 Aug 28;18(1):52. doi: 10.1186/s13062-023-00408-3.
Endothelial cell migration is a key process in angiogenesis. Progress of endothelial cell migration is orchestrated by coordinated generation of Ca signals through a mechanism organized in caveolar microdomains. Connexins (Cx) play a central role in coordination of endothelial cell function, directly by cell-to-cell communication via gap junction and, indirectly, by the release of autocrine/paracrine signals through Cx-formed hemichannels. However, Cx hemichannels are also permeable to Ca and Cx43 can be associated with caveolin-1, a structural protein of caveolae. We proposed that endothelial cell migration relies on Cx43 hemichannel opening. Here we show a novel mechanism of Ca signaling in endothelial cell migration. The Ca signaling that mediates endothelial cell migration and the subsequent tubular structure formation depended on Cx43 hemichannel opening and is associated with the translocation of Cx43 with caveolae to the rear part of the cells. These findings indicate that Cx43 hemichannels play a central role in endothelial cell migration and provide new therapeutic targets for the control of deregulated angiogenesis in pathological conditions such as cancer.
内皮细胞迁移是血管生成的关键过程。内皮细胞迁移的进展是通过在小窝微域中组织的协调机制通过协调的 Ca 信号产生来协调的。连接蛋白 (Cx) 通过缝隙连接通过细胞间通讯直接在协调内皮细胞功能中起核心作用，并且通过 Cx 形成的半通道通过自分泌/旁分泌信号间接起作用。然而，Cx 半通道也对 Ca 具有通透性，并且 Cx43 可以与 caveolin-1（小窝的结构蛋白）相关联。我们提出内皮细胞迁移依赖于 Cx43 半通道的开放。在这里，我们展示了内皮细胞迁移中 Ca 信号转导的新机制。介导内皮细胞迁移和随后管状结构形成的 Ca 信号取决于 Cx43 半通道的开放，并与 Cx43 与 caveolae 向细胞后部的易位相关。这些发现表明 Cx43 半通道在内皮细胞迁移中起核心作用，并为控制病理性条件（如癌症）中失调的血管生成提供了新的治疗靶点。
