Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada; and.
Am J Physiol Cell Physiol. 2014 Feb 15;306(4):C307-19. doi: 10.1152/ajpcell.00226.2013. Epub 2013 Nov 6.
Efficient repair of epithelial tissue, which is frequently exposed to insults, is necessary to maintain its functional integrity. It is therefore necessary to better understand the biological and molecular determinants of tissue regeneration and to develop new strategies to promote epithelial repair. Interestingly, a growing body of evidence indicates that many members of the large and widely expressed family of K(+) channels are involved in regulation of cell migration and proliferation, key processes of epithelial repair. First, we briefly summarize the complex mechanisms, including cell migration, proliferation, and differentiation, engaged after epithelial injury. We then present evidence implicating K(+) channels in the regulation of these key repair processes. We also describe the mechanisms whereby K(+) channels may control epithelial repair processes. In particular, changes in membrane potential, K(+) concentration, cell volume, intracellular Ca(2+), and signaling pathways following modulation of K(+) channel activity, as well as physical interaction of K(+) channels with the cytoskeleton or integrins are presented. Finally, we discuss the challenges to efficient, specific, and safe targeting of K(+) channels for therapeutic applications to improve epithelial repair in vivo.
高效修复经常受到外界刺激的上皮组织对于维持其功能完整性是必要的。因此，有必要更好地了解组织再生的生物学和分子决定因素，并开发新的策略来促进上皮修复。有趣的是，越来越多的证据表明，广泛表达的 K(+) 通道大家族中的许多成员参与了细胞迁移和增殖的调节，这是上皮修复的关键过程。首先，我们简要总结了上皮损伤后涉及的复杂机制，包括细胞迁移、增殖和分化。然后，我们提出了 K(+) 通道参与调节这些关键修复过程的证据。我们还描述了 K(+) 通道控制上皮修复过程的机制。特别是，在调节 K(+) 通道活性后，膜电位、K(+) 浓度、细胞体积、细胞内 Ca(2+) 和信号通路的变化，以及 K(+) 通道与细胞骨架或整合素的物理相互作用都被提出。最后，我们讨论了针对 K(+) 通道进行有效、特异和安全的靶向治疗以改善体内上皮修复的挑战。
