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The Whey Acidic Protein WFDC12 Is Specifically Expressed in Terminally Differentiated Keratinocytes and Regulates Epidermal Serine Protease Activity

Authors :
Lucian Beer
Polina Kalinina
Adelheid Elbe-Bürger
Alain Hovnanian
Vera Vorstandlechner
Michael Mildner
Erwin Tschachler
Barbara Sterniczky
Leopold Eckhart
Dagmar Födinger
Barbara Lengauer
Maria Laggner
Evgeniya Petrova
Bahar Golabi
Maria Buchberger
Manuela Hiess
Source :
The Journal of investigative dermatology. 141(5)
Publication Year :
2020

Abstract

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.

Details

ISSN :
15231747
Volume :
141
Issue :
5
Database :
OpenAIRE
Journal :
The Journal of investigative dermatology
Accession number :
edsair.doi.dedup.....67528d803e1bc1510a3c9510ec1334c2