Homeostatic Function of Dermokine in the Skin Barrier and Inflammation

Abstract

Dermokine is a chiefly skin-specific secreted glycoprotein localized in the upper epidermis, and its family consists of three splice variants in mice and five in humans. To investigate the pathophysiological impact of dermokine, we generated mice deficient for two (bg) or all dermokine isoforms (abg). Both variants, especially dermokine abg-deficient mice exhibited scale and wrinkle formation resembling ichthyosis accompanied by transepidermal water imbalance at the neonatal stage. Several dermokine abg-deficient mice died by postnatal day 21 when reared under low humidity. Moreover, the cornified envelope was vulnerable, and skin barrier lipid ceramides were reduced in the epidermis of dermokine abg-deficient mice. cDNA microarray and quantitative reverse transcriptaseePCR assays of the epidermis revealed the upregulation of small proline-rich protein and late cornified envelope family members, as well as antimicrobial peptides in the dermokine abg-deficient mice. These barrier gene signatures were similar to that seen in psoriasis, whereas recent studies demonstrated that congenital ichthyosis has gene profiles resembling psoriasis. In line with these findings, adult dermokine abg-deficient mice exhibited aggravated phenotypes in psoriasis-like dermatitis models but not in allergic dermatitis models. Dermokine may play a regulatory role in inflammatory dyskeratotic diseases, such as congenital ichthyosis and psoriasis, in the crosstalk between barrier dysfunction and inflammation.

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

“…When additional gene editing or post-transcription interference (i.e., knockdown) methods are applied, complex mechanisms may be illuminated as recently shown for the role of epigenetic hydroxymethylation on S100A9 expression in the IMQ model [213] or the impact of dermokines (DMKN) in skin inflammation and barrier function [214].…”

Discovery of Natural Bispecific Antibodies: Is Psoriasis Induced by a ToxigenicCorynebacterium simulansand Maintained by CIDAMPs as Autoantigens?

“…Here the epidermal protein dermokine was identified as autoantigen revealing three epitopes. It is of note that dermokine αβγ-deficient mice exhibited aggravated phenotypes in psoriasis-like dermatitis models, and showed barrier gene signatures similar to that seen in psoriasis 76 . A deficiency of dermokine leads to a transient cornification defect 77 .…”

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

“…Therefore, the transcriptome pro ling of the EMT/VM-mediated treatment-resistant samples could be a valuable strategy for nding exceptional responders to the personalized melanoma therapy 9,10 .Recently, researchers tried to nd novel VM/EMT-targeted therapeutic genes that are differentially regulated during melanomagenesis. One of the identi ed genes was a recently-reported skin-speci c gene, phosphatidylserine-speci c phospholipase A1-alpha (PLA1A) and dermokine (DMKN) that contribute to melanomagenesis by triggering the EMT signaling pathway and VM formation 11,12 . These genes can be transcriptionally used as promising biomarkers for exceptional responders in the targeted melanoma therapy 12 .…”