Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile.
Programa de Doctorado en Ciencias, Mención Neurociencia, Universidad de Valparaíso, Valparaíso 2340000, Chile.
Int J Mol Sci. 2021 Jan 22;22(3):1069. doi: 10.3390/ijms22031069.
Wound healing is a dynamic process required to maintain skin integrity and which relies on the precise migration of different cell types. A key molecule that regulates this process is ATP. However, the mechanisms involved in extracellular ATP management are poorly understood, particularly in the human dermis. Here, we explore the role, in human fibroblast migration during wound healing, of Pannexin 1 channels and their relationship with purinergic signals and in vivo cell surface filamentous actin dynamics. Using siRNA against Panx isoforms and different Panx1 channel inhibitors, we demonstrate in cultured human dermal fibroblasts that the absence or inhibition of Panx1 channels accelerates cell migration, increases single-cell motility, and promotes actin redistribution. These changes occur through a mechanism that involves the release of ATP to the extracellular space through a Panx1-dependent mechanism and the activation of the purinergic receptor P2X7. Together, these findings point to a pivotal role of Panx1 channels in skin fibroblast migration and suggest that these channels could be a useful pharmacological target to promote damaged skin healing.
伤口愈合是维持皮肤完整性所必需的动态过程，依赖于不同细胞类型的精确迁移。调节这个过程的关键分子是 ATP。然而，细胞外 ATP 管理涉及的机制还了解甚少，特别是在人类真皮中。在这里，我们探讨了 Pannexin 1 通道在人类成纤维细胞迁移中的作用及其与嘌呤能信号的关系，以及体内细胞表面丝状肌动蛋白动力学。使用针对 Panx 同种型的 siRNA 和不同的 Panx1 通道抑制剂，我们在培养的人真皮成纤维细胞中证明，Pannexin 1 通道的缺失或抑制会加速细胞迁移，增加单细胞迁移率，并促进肌动蛋白重新分布。这些变化是通过一种机制发生的，该机制涉及通过 Panx1 依赖性机制将 ATP 释放到细胞外空间，以及嘌呤能受体 P2X7 的激活。这些发现共同表明 Panx1 通道在皮肤成纤维细胞迁移中起着关键作用，并表明这些通道可能是促进受损皮肤愈合的有用的药理学靶点。
