Troy Tammy-Claire, Li Yuhua, O'Malley Lauren, Turksen Kursad
Ottawa Health Research Institute, University of Ottawa, Ottawa, Ont., Canada.
Gene Expr Patterns. 2007 Feb;7(4):423-30. doi: 10.1016/j.modgep.2006.11.006. Epub 2006 Nov 19.
The importance of the epidermal permeability barrier (EPB) in protecting the mammalian species against harmful UV irradiation, microorganism invasion and water loss is well recognized, as is the role of calcium (Ca(2+)) in keratinocyte differentiation, cell-cell contact and the EPB. In a previous study, we reported that the overexpression of the Ca(2+)-sensing receptor (CaSR) in the undifferentiated basal cells of the epidermis induced a modified epidermal differentiation program including an accelerated EPB formation in transgenic mice, suggesting a role for CaSR signaling in the differentiation of embryonic epidermal cells during development. We now describe the expression profile of claudins (Cldns) and keratin markers in the accelerated EPB formation of K14-CaSR transgenic mice during development as compared to the wild type from E12.5 to newborn stages. Our data show that the transgenic epidermis undergoes an advanced epidermal differentiation program as compared to the wild type as evidenced morphologically as well as by the expression of K14, K1, loricrin, Cldn6, Cldn18 and Cldn11. In addition, we report for the first time the sequential expression of Cldns in epidermal development and describe that the localization of some Cldns change within the epidermis as it matures. Furthermore, we demonstrate that Cldn6 is expressed very early in epidermal morphogenesis, followed by Cldn18, Cldn11 and Cldn1.
表皮通透屏障(EPB)在保护哺乳动物免受有害紫外线辐射、微生物入侵和水分流失方面的重要性已得到充分认识,钙(Ca(2+))在角质形成细胞分化、细胞间接触和EPB中的作用也同样如此。在先前的一项研究中,我们报道了在表皮未分化的基底细胞中钙敏感受体(CaSR)的过表达诱导了一种改变的表皮分化程序,包括转基因小鼠中EPB形成加速,这表明CaSR信号在发育过程中胚胎表皮细胞的分化中发挥作用。我们现在描述了与野生型相比,从E12.5到新生阶段发育过程中K14-CaSR转基因小鼠加速形成EPB时紧密连接蛋白(Cldns)和角蛋白标志物的表达谱。我们的数据表明,与野生型相比,转基因表皮经历了一个先进的表皮分化程序,这在形态学上以及通过K14、K1、兜甲蛋白、Cldn6、Cldn18和Cldn11的表达得到了证实。此外,我们首次报道了Cldns在表皮发育中的顺序表达,并描述了随着表皮成熟,一些Cldns在表皮内的定位发生变化。此外,我们证明Cldn6在表皮形态发生的早期就有表达,随后是Cldn18、Cldn11和Cldn1。