Homeostatic Function of Dermokine in the Skin Barrier and Inflammation

Akira Utsunomiya, Takenao Chino, Natsuko Utsunomiya, Vu Huy Luong, Atsushi Tokuriki, Tatsuro Naganuma, Makoto Arita, Kiyoshi Higashi, Koichi Saito, Noriyuki Suzuki, Ayako Ohara, Manabu Sugai, Koji Sugawara, Daisuke Tsuruta, Noritaka Oyama, Minoru Hasegawa

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1 Citation (Scopus)

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 (βγ) or all dermokine isoforms (αβγ). Both variants, especially dermokine αβγ-deficient mice exhibited scale and wrinkle formation resembling ichthyosis accompanied by transepidermal water imbalance at the neonatal stage. Several dermokine αβγ-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 αβγ-deficient mice. cDNA microarray and quantitative reverse transcriptase–PCR 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 αβγ-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 αβγ-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.

Original languageEnglish
Pages (from-to)838-849.e9
JournalJournal of Investigative Dermatology
Volume140
Issue number4
DOIs
Publication statusPublished - 2020 Apr

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Utsunomiya, A., Chino, T., Utsunomiya, N., Luong, V. H., Tokuriki, A., Naganuma, T., Arita, M., Higashi, K., Saito, K., Suzuki, N., Ohara, A., Sugai, M., Sugawara, K., Tsuruta, D., Oyama, N., & Hasegawa, M. (2020). Homeostatic Function of Dermokine in the Skin Barrier and Inflammation. Journal of Investigative Dermatology, 140(4), 838-849.e9. https://doi.org/10.1016/j.jid.2019.09.011