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首页> 外文期刊>The Journal of investigative dermatology. >25 Hydroxyvitamin D 1 alpha-Hydroxylase Is Required for Optimal Epidermal Differentiation and Permeability Barrier Homeostasis.
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25 Hydroxyvitamin D 1 alpha-Hydroxylase Is Required for Optimal Epidermal Differentiation and Permeability Barrier Homeostasis.

机译：25羟基维生素D 1α-羟化酶是最佳表皮分化和渗透屏障动态平衡所必需的。

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Keratinocytes express high levels of 25OHD 1alpha-hydroxylase (1OHase). The product of this enzyme, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), promotes the differentiation of keratinocytes in vitro suggesting an important role for this enzyme in epidermal differentiation. To test whether 1OHase activity is essential for keratinocyte differentiation in vivo we examined the differentiation process in mice null for the expression of the 1alphaOHase gene (1alphaOHase(-/-)). Heterozygotes for the null allele were bred, and the progeny genotyped by PCR. The epidermis of the 1alphaOHase(-/-) animals and their wild-type littermates (1alphaOHase(+/+)) were examined by histology at the light and electron microscopic level, by immunocytochemistry for markers of differentiation, and by function examining the permeability barrier using transepidermal water loss (TEWL). No gross epidermal phenotype was observed; however, immunocytochemical assessment of the epidermis revealed a reduction in involucrin, filaggrin, and loricrin-markers of differentiation in the keratinocyte and critical for the formation of the cornified envelope. These observations were confirmed at the electron microscopic level, which showed a reduction in the F (containing filaggrin) and L (containing loricrin) granules and a reduced calcium gradient. The functional significance of these observations was tested using TEWL to evaluate the permeability barrier function of the epidermis. Although TEWL was normal in the basal state, following disruption of the barrier using tape stripping, the 1alphaOHase(-/-) animals displayed a markedly delayed recovery of normal barrier function. This delay was associated with a reduction in lamellar body secretion and a failure to reform the epidermal calcium gradient. Thus, the 25OHD 1OHase is essential for normal epidermal differentiation, most likely by producing the vitamin D metabolite, 1,25(OH)(2)D, responsible for inducing the proteins regulating calcium levels in the epidermis that are critical for the generation and maintenance of the barrier.
机译：角质形成细胞表达高水平的25OHD1α-羟化酶（1OHase）。该酶的产物1,25-二羟基维生素D（1,25（OH）（2）D）在体外促进角质形成细胞的分化，提示该酶在表皮分化中起重要作用。为了测试1OHase活性对于体内角质形成细胞的分化是否必要，我们检查了1alphaOHase基因（1alphaOHase（-/-））表达无效的小鼠的分化过程。繁殖出无效等位基因的杂合子，并通过PCR对后代进行基因分型。通过光和电子显微镜下的组织学检查，通过免疫细胞化学法鉴定分化标志物以及通过检查通透性的功能检查1alphaOHase（-/-）动物及其野生型同窝动物（1alphaOHase（+ / +））的表皮使用表皮失水（TEWL）的屏障。没有观察到大的表皮表型。然而，对表皮的免疫细胞化学评估显示，角质形成细胞分化中的囊泡蛋白，丝蛋白和loricrin标记减少，这对于形成角质化包膜至关重要。这些观察结果在电子显微镜下得到证实，其显示出F（含丝聚蛋白）和L（含洛瑞林）颗粒的减少和钙梯度的减少。使用TEWL评估了这些观察的功能意义，以评估表皮的通透屏障功能。尽管TEWL在基础状态下是正常的，但使用胶带剥离破坏屏障后，1alphaOHase（-/-）动物显示出正常屏障功能的恢复明显延迟。这种延迟与层状体分泌减少和未能改变表皮钙梯度有关。因此，25OHD 1OHase对于正常的表皮分化是必不可少的，很可能是通过产生维生素D代谢物1,25（OH）（2）D来引起的，该代谢物负责诱导调节表皮中钙水平的蛋白质，这对于生成和代谢至关重要。维护屏障。

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