Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo 142-8555, Japan;
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):12243-12248. doi: 10.1073/pnas.1710726114. Epub 2017 Oct 23.
Skin tissues, in particular the epidermis, are severely affected by zinc deficiency. However, the zinc-mediated mechanisms that maintain the cells that form the epidermis have not been established. Here, we report that the zinc transporter ZIP10 is highly expressed in the outer root sheath of hair follicles and plays critical roles in epidermal development. We found that ZIP10 marked epidermal progenitor cell subsets and that ablating caused significant epidermal hypoplasia accompanied by down-regulation of the transactivation of p63, a master regulator of epidermal progenitor cell proliferation and differentiation. Both ZIP10 and p63 are significantly increased during epidermal development, in which ZIP10-mediated zinc influx promotes p63 transactivation. Collectively, these results indicate that ZIP10 plays important roles in epidermal development via, at least in part, the ZIP10-zinc-p63 signaling axis, thereby highlighting the physiological significance of zinc regulation in the maintenance of skin epidermis.
皮肤组织，特别是表皮，受到锌缺乏的严重影响。然而，维持表皮细胞的锌介导机制尚未建立。在这里，我们报告锌转运蛋白 ZIP10 在毛囊外根鞘中高度表达，并在表皮发育中发挥关键作用。我们发现 ZIP10 标记表皮祖细胞亚群，并且缺失导致明显的表皮发育不良，伴随着 p63 的转录激活下调，p63 是表皮祖细胞增殖和分化的主调控因子。在表皮发育过程中，ZIP10 和 p63 均显著增加，其中 ZIP10 介导的锌内流促进 p63 的转录激活。总之，这些结果表明 ZIP10 通过至少部分 ZIP10-锌-p63 信号轴在表皮发育中发挥重要作用，从而强调了锌调节在维持皮肤表皮中的生理意义。
