Knockouts of both Vitamin D receptor (VDR) and its coactivator Med1 enhance epidermal permeability barrier function

Vitamin D receptor (VDR) is crucial for formation of epidermal permeability barrier and ceramide production, while mediator complex subunit 1 (Med1), a coactivator of VDR, mediates the action of VDR. VDR deficiency compromises epidermal permeability barrier in mice. Hence, we are investigating the dual role of VDR and Med1 in epidermal permeability barrier. Mice with VDR and Med1 specifically deleted in Keratin 14 expressing keratinocytes (DKO) by Cre-lox strategy are utilized. The mice with both floxed VDR and Med1 but no Cre serve as control. The data showed here that knockouts of both VDR and Med1 enhanced epidermal permeability barrier in mice, accompanied by increased expression levels of mRNA for keratinocyte differentiation marker-related proteins, fatty acid and ceramide productions, which all are required for formation of epidermal permeability barrier. Moreover, expression levels of mRNA for ceramide transporter (ABCA12) were also elevated in DKO mice vs. knockout of either VDR or Med1 alone. Collectively, these results demonstrate that knockouts of both VDR and Med1 enhance epidermal permeability barrier function via upregulating expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes, suggesting additional signaling pathway(s) involve regulatory role of VDR/Med1 in epidermal function. Epidermal mRNA profiles of P36 and 6-month-old VDR and Med1 double knockout and control mice维生素D受体（Vitamin D receptor, VDR）在皮肤表皮通透屏障的形成及神经酰胺生成过程中发挥关键作用；中介复合体亚基1（Mediator Complex Subunit 1, Med1）作为VDR的共激活因子，可介导VDR的生物学功能。小鼠体内VDR缺失会损伤表皮通透屏障功能。为此，本研究旨在探究VDR与Med1在表皮通透屏障中的双重调控作用。本研究通过Cre-lox重组技术，构建了在表达角蛋白14（Keratin 14）的角质形成细胞中特异性敲除VDR与Med1的双敲除（DKO）小鼠模型，同时以仅携带floxed VDR和floxed Med1但无Cre重组酶的小鼠作为对照。本研究所得数据显示，同时敲除VDR与Med1可增强小鼠的表皮通透屏障功能，伴随角质形成细胞分化标记相关蛋白、脂肪酸及神经酰胺合成相关基因的mRNA表达水平上调——上述产物均为表皮通透屏障形成所必需。此外，与单独敲除VDR或Med1的小鼠相比，双敲除小鼠体内神经酰胺转运蛋白（ABCA12）的mRNA表达水平同样显著升高。综上，上述结果表明，同时敲除VDR与Med1可通过上调表皮分化标记相关蛋白及脂质合成酶的mRNA表达水平，增强小鼠的表皮通透屏障功能，这提示VDR/Med1调控表皮功能的信号通路尚存在其他未被阐明的途径。本数据集涵盖36日龄及6月龄的VDR与Med1双敲除小鼠和对照小鼠的表皮mRNA表达谱。