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- W4237980979 abstract "It is suggested that kallikrein-related peptidases (KLKs) are key players in corneocyte desquamation and this process is regulated by lympho-epithelial Kazal-type inhibitor (LEKTI). However, it is unclear how these proteases are activated and how activated KLKs are released from LEKTI in the upper cornified layer. Previously we reported cloning of a new PRSS3 gene product, keratinocyte-specific mesotrypsin from the cDNA library. It has been reported that mesotrypsin is insusceptible to intrinsic inhibitors. Moreover, we found that mesotrypsin effectively activated pro-KLK5 and pro-KLK7. Although LEKTI strongly inhibited KLKs, mesotrypsin was not suppressed by LEKTI but rather degraded them. Surprisingly, we isolated a novel inhibitor and identified it as serpinB12 (Another name is YUKOPIN). Thin skin, such as the eyelid, showed strong mesotrypsin staining, while serpinB12 staining was barely detectable. In contrast, footpad skin, which has a thick cornified layer, showed strong serpinB12 staining at the granular layer. We constructed skin equivalent models, in which serpinB12 was over-expressed or knocked-down. Cornified layers were increased and the epidermis became thicker in serpinB12 over-expression. When serpinB12 was down-regulated, the epidermal structure became very thin. Furthermore, we found that excessive over-expression of serpinB12 induced parakeratosis. Immunohistochemical study showed that serpinB12 was expressed in parakeratic area of diseased skin, such as psoriasis and atopic dermatitis. Our findings provided a new insight into the desquamation mechanisms, in which mesotrypsin and serpinB12 play critical roles. Moreover, our results suggest that serpinB12 would be involved in controlling the thickness of stratum corneum through mesotrypsin regulation, and excessive serpinB12 expression might be the cause of parakeratotic disease condition." @default.
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- W4237980979 date "2019-05-01" @default.
- W4237980979 modified "2023-09-26" @default.
- W4237980979 title "286 SerpinB12 is an intrinsic mesotrypsin inhibitor regulating corneocyte desquamation and denucleation" @default.
- W4237980979 doi "https://doi.org/10.1016/j.jid.2019.03.362" @default.
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