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Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, besides the immune system cells. However, the role of CatE in these cells r...emains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induced 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 resulted in the significantly reduced expression and altered localization of the keratinocyte differentiation-induced proteins keratin 1 and loricrin. The link of CatE to 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 the wild-type keratinocytes after differentiation-inducing stimuli, the expression profile of CatE gene was compatible with those of the terminal differentiation marker genes tested. Over-expression of CatE in mice enhanced the rate of keratinocyte terminal differentiation process, whereas CatE deficiency resulted in the delayed differentiation accompanying the reduced expression or the ectopic localization of the differentiation markers. Our findings suggest that CatE in keratinocytes functionally links to the expression of the terminal differentiation markers, thereby regulating the formation and homeostasis of the epidermis.続きを見る
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