Eye Institute of Xiamen University, Xiamen, Fujian, China.
Medical College of Xiamen University, Xiamen, Fujian, China.
J Cell Mol Med. 2018 Jan;22(1):230-240. doi: 10.1111/jcmm.13311. Epub 2017 Aug 7.
Ectodysplasin A (Eda), a member of the tumour necrosis factor superfamily, plays an important role in ectodermal organ development. An EDA mutation underlies the most common of ectodermal dysplasias, that is X-linked hypohidrotic ectodermal dysplasia (XLHED) in humans. Even though it lacks a developmental function, the role of Eda during the postnatal stage remains elusive. In this study, we found tight junctional proteins ZO-1 and claudin-1 expression is largely reduced in epidermal, corneal and lung epithelia in Eda mutant Tabby mice at different postnatal ages. These declines are associated with tail ulceration, corneal pannus formation and lung infection. Furthermore, topical application of recombinant Eda protein markedly mitigated corneal barrier dysfunction. Using cultures of a human corneal epithelial cell line and Tabby mouse skin tissue explants, Eda up-regulated expression of ZO-1 and claudin-1 through activation of the sonic hedgehog signalling pathway. We conclude that EDA gene expression contributes to the maintenance of epithelial barrier function. Such insight may help efforts to identify novel strategies for improving management of XLHED disease manifestations in a clinical setting.
外胚层发育不全蛋白 A（Eda）是肿瘤坏死因子超家族的成员，在表皮器官发育中发挥重要作用。EDA 突变是最常见的外胚层发育不全的基础，即人类的 X 连锁少汗性外胚层发育不全（XLHED）。尽管它缺乏发育功能，但 Eda 在出生后的作用仍然难以捉摸。在这项研究中，我们发现紧密连接蛋白 ZO-1 和 Claudin-1 的表达在不同出生后年龄的 Tabby 突变小鼠的表皮、角膜和肺上皮中大量减少。这些下降与尾部溃疡、角膜血管翳形成和肺部感染有关。此外，重组 Eda 蛋白的局部应用显著减轻了角膜屏障功能障碍。使用人角膜上皮细胞系和 Tabby 小鼠皮肤组织外植体的培养，Eda 通过激活 sonic hedgehog 信号通路上调 ZO-1 和 Claudin-1 的表达。我们得出结论，EDA 基因表达有助于维持上皮屏障功能。这种见解可能有助于努力确定在临床环境中改善 XLHED 疾病表现的新策略。
