The ENaC channel is required for normal epidermal differentiation

The ENaC channel is required for normal epidermal differentiation
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DOI:
10.1046/j.1523-1747.2002.01721.x
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发表时间:
2002-04-01
影响因子:
6.5
通讯作者:
Hummler, E
Hummler, E
中科院分区:
医学1区
文献类型:
--
作者:
Mauro, T;Guitard, M;Hummler, E

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离子通量对于角质形成细胞分化的关键方面非常重要,包括分化特异性蛋白质的合成、蛋白质交联的酶催化、聚丝蛋白原的转录后加工和脂质分泌。上皮钠通道在表皮中表达,并且其α和β亚基的表达随着角质形成细胞的分化而增强。为了确定上皮钠通道在表皮分化中的作用,我们检查了上皮钠通道α亚基已被删除的小鼠皮肤。 α亚基完全失活的新生-/-小鼠表现出上皮增生、细胞核异常、脂质过早分泌和角质透明颗粒异常。此外,免疫组织化学显示分化标志物K1、K6和外皮蛋白的表达异常。这些数据表明上皮钠通道调节表皮分化特定方面的离子信号传导,例如分化特异性蛋白质的合成或加工以及脂质分泌。
Ionic fluxes are important for critical aspects of keratinocyte differentiation, including synthesis of differentiation-specific proteins, enzymatic catalysis of protein cross-linking, post-transcriptional processing of profilaggrin, and lipid secretion. The epithelial sodium channel is expressed in epidermis and the expression of its alpha and beta subunits is enhanced as keratinocytes differentiate. In order to ascertain the role of the epithelial sodium channel in epidermal differentiation, we examined skin of mice in which the epithelial sodium channel alpha subunit had been deleted. Newborn -/- mice, in which the alpha subunit had been completely inactivated, demonstrated epithelial hyperplasia, abnormal nuclei, premature secretion of lipids, and abnormal keratohyaline granules. In addition, immunohistochemistry demonstrated that expression of the differentiation markers K1, K6, and involucrin were abnormal. These data suggest that the epithelial sodium channel modulates ionic signaling for specific aspects of epidermal differentiation, such as synthesis or processing of differentiation-specific proteins, and lipid secretion.