The Finsen Laboratory, Copenhagen University Hospital (Rigshospitalet), Copenhagen Biocenter, Copenhagen, Denmark.
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Biomed Res Int. 2017;2017:2403072. doi: 10.1155/2017/2403072. Epub 2017 Sep 7.
A multi-LU-domain-containing protein denoted C4.4A exhibits a tightly regulated membrane-associated expression in the suprabasal layers of stratified squamous epithelia such as skin and the esophagus, and the expression of C4.4A is dysregulated in various pathological conditions. However, the biological function of C4.4A remains unknown. To enable further studies, we evaluated the expression of C4.4A in monolayer cultures of normal human keratinocytes and in tissue-engineered skin substitutes (TESs) produced by the self-assembly approach, which allow the formation of a fully differentiated epidermis tissue. Results showed that, in monolayer, C4.4A was highly expressed in the centre of keratinocyte colonies at cell-cell contacts areas, while some cells located at the periphery presented little C4.4A expression. In TES, emergence of C4.4A expression coincided with the formation of the After the creation of a wound within the TES, C4.4A expression was observed in the suprabasal keratinocytes of the migrating epithelium, with the exception of the foremost leading keratinocytes, which were negative for C4.4A. Our results are consistent with previous data in mouse embryogenesis and wound healing. Based on these findings, we conclude that this human TES model provides an excellent surrogate for studies of C4.4A and Haldisin expressions in human stratified epithelia.
一种多 LU 结构域蛋白 C4.4A 在皮肤和食管等分层鳞状上皮的基底层呈现出严格调控的膜相关表达，并且 C4.4A 的表达在各种病理条件下失调。然而，C4.4A 的生物学功能仍然未知。为了进行进一步的研究，我们评估了 C4.4A 在正常人类角质形成细胞的单层培养物和通过自组装方法产生的组织工程皮肤替代物（TESs）中的表达，该方法允许形成完全分化的表皮组织。结果表明，在单层培养物中，C4.4A 在细胞-细胞接触区域的角质形成细胞菌落的中心高度表达，而位于外围的一些细胞表达很少的 C4.4A。在 TES 中，C4.4A 的表达与表皮的形成一致。在 TES 内形成伤口后，C4.4A 在迁移上皮的基底层角质形成细胞中表达，除了最前沿的主导角质形成细胞外，它们对 C4.4A 呈阴性。我们的结果与以前在小鼠胚胎发生和伤口愈合中的数据一致。基于这些发现，我们得出结论，这种人类 TES 模型为研究人类分层上皮中的 C4.4A 和 Haldisin 表达提供了一个极好的替代物。
