The epidermal barrier function is dependent on the serine protease CAP1/Prss8.
The epidermal barrier function is dependent on the serine protease CAP1/Prss8.
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DOI：
10.1083/jcb.200501038
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发表时间：
2005-08-01
影响因子：
7.8
通讯作者：
Hummler, Edith
中科院分区：
文献类型：
--
作者：
Leyvraz, Celine;Charles, Roch-Philippe;Rubera, Isabelle;Guitard, Marjorie;Rotman, Samuel;Breiden, Bernadette;Sandhoff, Konrad;Hummler, Edith
丝氨酸蛋白酶是参与多种生理过程调节的蛋白水解酶。我们培育出皮肤中缺乏膜锚定通道激活丝氨酸蛋白酶 (CAP) 1（也称为蛋白酶丝氨酸 S1 家族成员 8 [Prss8] 和前列腺素）的小鼠，这些小鼠在出生后 60 小时内死亡。他们的体重较低，并且角质层（SC）严重畸形。这种异常的皮肤发育伴随着皮肤屏障功能受损，脱水和皮肤渗透性测定以及经表皮失水测量导致快速致命的脱水证明了这一点。分化标记物分析显示，尽管表皮 CAP1/Prss8 表达缺陷扰乱了 SC 脂质组成、角质细胞形态发生和聚丝蛋白原加工，但 CAP1/Prss8 缺陷皮肤没有发生重大变化。紧密连接蛋白的检查显示不存在occludin，这并不能阻止皮下注射的示踪剂（∼600 D）向皮肤表面扩散。这项研究表明，表皮中的 CAP1/Prss8 表达对于表皮通透性屏障至关重要，因此对于出生后生存是不可或缺的。
Serine proteases are proteolytic enzymes that are involved in the regulation of various physiological processes. We generated mice lacking the membrane-anchored channel-activating serine protease (CAP) 1 (also termed protease serine S1 family member 8 [Prss8] and prostasin) in skin, and these mice died within 60 h after birth. They presented a lower body weight and exhibited severe malformation of the stratum corneum (SC). This aberrant skin development was accompanied by an impaired skin barrier function, as evidenced by dehydration and skin permeability assay and transepidermal water loss measurements leading to rapid, fatal dehydration. Analysis of differentiation markers revealed no major alterations in CAP1/Prss8-deficient skin even though the epidermal deficiency of CAP1/Prss8 expression disturbs SC lipid composition, corneocyte morphogenesis, and the processing of profilaggrin. The examination of tight junction proteins revealed an absence of occludin, which did not prevent the diffusion of subcutaneously injected tracer (∼600 D) toward the skin surface. This study shows that CAP1/Prss8 expression in the epidermis is crucial for the epidermal permeability barrier and is, thereby, indispensable for postnatal survival.