Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
J Cell Biol. 2018 Dec 3;217(12):4267-4283. doi: 10.1083/jcb.201804048. Epub 2018 Sep 18.
In epithelial tissues, cells tightly connect to each other through cell-cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process. We demonstrate that OJ loss of function leads to defects in wound-closure dynamics: instead of contracting, wounds dramatically increase their area. OJ mutants exhibit phenotypes in cell shape, cellular rearrangements, and mechanical properties as well as in actin cytoskeleton dynamics at the wound edge. We propose that OJs are essential for wound closure by impacting on epithelial mechanics at the tissue level, which in turn is crucial for correct regulation of the cellular events occurring at the wound edge.
在上皮组织中，细胞通过细胞-细胞连接紧密地连接在一起，但它们也具有在不损害组织完整性的情况下重新组织自身的显著能力。在受伤时，简单的上皮组织通过在伤口边缘处的肌动蛋白细胞骨架收缩结构和细胞重排来有效地解决小的损伤。然而，潜在的机制以及它们如何合作仍然知之甚少。在这项研究中，我们结合了实时成像和理论建模，揭示了封闭连接（OJ）在这个过程中的一个新的、不可或缺的作用。我们证明了 OJ 功能丧失会导致伤口闭合动力学的缺陷：伤口不是收缩，而是显著增大了面积。OJ 突变体在细胞形状、细胞重排以及机械性能以及伤口边缘处的肌动蛋白细胞骨架动力学方面表现出表型。我们提出，OJ 通过影响组织水平的上皮力学对于伤口闭合是必不可少的，这对于正确调节伤口边缘处发生的细胞事件至关重要。
