The role of cathepsin E in terminal differentiation of keratinocytes
The role of cathepsin E in terminal differentiation of keratinocytes
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DOI：
10.1515/bc.2011.060
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发表时间：
2011-04-01
影响因子：
3.7
通讯作者：
Yamamoto, Kenji
中科院分区：
文献类型：
--
作者：
Kawakubo, Tomoyo;Yasukochi, Atsushi;Yamamoto, Kenji
除了免疫系统细胞外，组织蛋白酶 E (CatE) 主要在快速再生的胃粘膜细胞和表皮角质形成细胞中表达。然而，CatE 在这些细胞中的作用仍不清楚。在这里，我们报道了 CatE 在角质形成细胞终末分化中的关键作用。小鼠CatE缺乏会导致表皮和毛囊角质形成细胞分化异常，其特征是真皮显着扩张，皮下组织和毛囊减少。在三种不同基因型同基因小鼠形成的皮肤乳头状瘤模型中，CatE 缺陷导致角质形成细胞分化诱导蛋白、角蛋白 1 和兜甲蛋白的表达显着降低并改变其定位。对三种不同基因型小鼠角质形成细胞原代培养物的体外研究证实了 CatE 参与表皮分化特异性蛋白表达的调节。在分化诱导刺激后的野生型角质形成细胞中，CatE 表达谱与所测试的终末分化标记基因的表达谱一致。小鼠中 CatE 的过度表达可增强角质形成细胞终末分化过程，而 CatE 缺乏会导致分化延迟，并伴有分化标记物表达减少或异位定位。我们的研究结果表明，在角质形成细胞中，CatE 在功能上与终末分化标记物的表达相关，从而调节表皮的形成和稳态。
Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induces abnormal keratinocyte differentiation in the epidermis and hair follicle, characterized by the significant expansion of corium and the reduction of subcutaneous tissue and hair follicle. In a model of skin papillomas formed in three different genotypes of syngeneic mice, CatE deficiency results in significantly reduced expression and altered localization of the keratinocyte differentiation induced proteins, keratin 1 and loricrin. Involvement of CatE in the regulation of the expression of epidermal differentiation specific proteins was corroborated by in vitro studies with primary cultures of keratinocytes from the three different genotypes of mice. In wild-type keratinocytes after differentiation inducing stimuli, the CatE expression profile was compatible to those of the terminal differentiation marker genes tested. Overexpression of CatE in mice enhances the keratinocyte terminal differentiation process, whereas CatE deficiency results in delayed differentiation accompanying the reduced expression or the ectopic localization of the differentiation markers. Our findings suggest that in keratinocytes CatE is functionally linked to the expression of terminal differentiation markers, thereby regulating epidermis formation and homeostasis.