Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.
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伤口修复模型中机械拉伸和共培养成纤维细胞下人类角质​​形成细胞的不对称迁移。

DOI:
10.1371/journal.pone.0074563
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Long M
Long M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lü D;Liu X;Gao Y;Huo B;Kang Y;Chen J;Sun S;Chen L;Luo X;Long M

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在生物化学和生物力学微环境下,再上皮化过程中的角质形成细胞迁移在伤口愈合中至关重要。然而,很少有人知道的基本机制,机械张力和共培养的成纤维细胞或角质形成细胞调节角质形成细胞或成纤维细胞的迁移。在这里,我们应用了一个拉伸装置连同一个修改的transwell测定,以确定横向和跨膜迁移动力学的人HaCaT角质形成细胞或HF成纤维细胞。当角质形成细胞与非接触性成纤维细胞共培养时,观察到一种新的不对称迁移模式,即,HaCaT细胞在远离HF细胞或自下而上穿过膜时的累积距离显著大于在靠近HF细胞或自上而下穿过膜时的累积距离,而HF细胞的迁移是对称的。这种不对称迁移主要受成纤维细胞来源的EGF调节,而不是转化生长因子α或β1的产生。机械拉伸受到成纤维细胞促进角质形成细胞的不对称迁移,通过增加表皮生长因子分泌,而没有发现机械拉伸角质形成细胞的表皮生长因子分泌的作用。这些结果为理解生物力学微环境下角质形成细胞或成纤维细胞沿着或跨真皮和表皮的二维或三维迁移的调控机制提供了新的见解。
Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.
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发表时间: 2002-08-01
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