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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Rho-dependent formation of epithelial 'leader' cells during wound healing
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Rho-dependent formation of epithelial 'leader' cells during wound healing

机译：伤口愈合过程中依赖Rho的上皮“前导”细胞形成

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摘要

The motile behavior of epithelial cells located at the edge of a large wound in a monolayer of cultured cells was analyzed. The initial cellular response is alignment of the edge with an accompanying formation of tangential marginal actin bundles within individual cells positioned along the wound edge. Later, coherent out-growths of cell masses occur by the formation of special "leader" cells at the tops of outgrowths and "follower" cells along the sides. Leader cells exhibit profound cytoskeletal reorganization, including disassembly of marginal bundles, the realignment of actin filament bundles, and penetration of microtubules into highly active lamellae. Additionally, cell-cell contacts acquire radial geometry indicative of increased contractile tension. Interestingly, leader cells acquire a cytoskeletal organization and motility typical of fibroblasts. IAR-2 cultures stably transfected with a dominant-negative mutant of RhoA or treated with Rho-kinase inhibitor Y-27632 transformed most edge cells into leader-like cells. Alternatively, transfection of cells with constitutively active RhoA suppressed formation of leaders. Thus, expansion of the epithelial sheet involves functional differentiation into two distinct types of edge cells. The transition between these two patterns is controlled by Rho activity, which in turn controls the dynamic distribution and activity of actin filament bundles, myosin II, and microtubules. [References: 34]
机译：分析了单层培养细胞中位于大伤口边缘的上皮细胞的运动行为。最初的细胞反应是将边缘与沿伤口边缘定位的单个细胞内切向边缘肌动蛋白束的伴随形成对齐。后来，细胞团的连贯生长通过在生长的顶部形成特殊的“前导”细胞和沿着侧面的“跟随”细胞而形成。前导细胞表现出深刻的细胞骨架重组，包括边缘束的解体，肌动蛋白丝束的重新排列以及微管向高活性薄片的渗透。另外，细胞-细胞接触获得指示增加的收缩张力的径向几何形状。有趣的是，前导细胞获得了成纤维细胞典型的细胞骨架组织和运动能力。用RhoA的显性阴性突变体稳定转染或用Rho激酶抑制剂Y-27632处理的IAR-2培养物将大多数边缘细胞转化为前导样细胞。或者，用组成型活性RhoA转染细胞可抑制前导细胞的形成。因此，上皮层的扩张涉及功能分化成两种不同类型的边缘细胞。这两种模式之间的过渡受Rho活性控制，Rho活性又控制肌动蛋白丝束，肌球蛋白II和微管的动态分布和活性。 [参考：34]

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