SLPI
弹力素
角质形成细胞
角质层
激肽释放酶
总苞素
下调和上调
蛋白酵素
丝状蛋白
洛里克林
脱皮
分子生物学
蛋白酶
弹性蛋白酶
生物化学
中性粒细胞弹性蛋白酶
丝氨酸蛋白酶
细胞生物学
角蛋白
生物
表皮(动物学)
表皮生长因子
丝氨酸
哈卡特
特应性皮炎
免疫学
细胞培养
炎症
酶
病理
基因
医学
解剖
古生物学
遗传学
作者
Polina Kalinina,Vera Vorstandlechner,Maria Buchberger,Leopold Eckhart,Barbara Lengauer,Bahar Golabi,Maria Laggner,Manuela Hiess,Barbara Sterniczky,Dagmar Födinger,Evgeniya Petrova,Adelheid Elbe-Bürger,Lucian Beer,Alain Hovnanian,Erwin Tschachler,Michael Mildner
标识
DOI:10.1016/j.jid.2020.09.025
摘要
WFDC proteins such as peptidase inhibitor 3 and SLPI inhibit proteases in the epidermis and other tissues. In this study, we tested the hypothesis that further WFDC protein family members might contribute to epidermal homeostasis. We found that in addition to peptidase inhibitor 3 and SLPI, WFDC5 and WFDC12 were expressed in human epidermis. In contrast to WFDC5, the expression of WFDC12 was induced during the late differentiation of keratinocytes and was restricted to the outermost layer of live cells. Single-cell RNA sequencing demonstrated that WFDC12-positive keratinocytes were characterized by the upregulation of LCE mRNA expression and downregulated the expression of keratins and claudins. Immunogold-electron microscopy revealed the colocalization of WFDC12 with corneodesmosomes in the lower stratum corneum. WFDC12 was elevated in the affected skin of patients with psoriasis, atopic dermatitis, and Darier disease. By contrast, WFDC12 expression was strongly upregulated not only in the affected but even more so in clinically normal-appearing skin of patients with Netherton syndrome. Finally, functional analysis showed distinct inhibitory activity of WFDC12 on neutrophil elastase and epidermal kallikrein‒related peptidase. Altogether, our study identified WFDC12 as a marker of the last stage of epidermal keratinocyte differentiation and suggests that WFDC12 contributes to the control of protease activity in the stratum corneum.
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