| First Author | Utsunomiya A | Year | 2020 |
| Journal | J Invest Dermatol | Volume | 140 |
| Issue | 4 | Pages | 838-849.e9 |
| PubMed ID | 31669414 | Mgi Jnum | J:297240 |
| Mgi Id | MGI:6441649 | Doi | 10.1016/j.jid.2019.09.011 |
| Citation | Utsunomiya A, et al. (2020) Homeostatic Function of Dermokine in the Skin Barrier and Inflammation. J Invest Dermatol 140(4):838-849.e9 |
| abstractText | 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 (betagamma) or all dermokine isoforms (alphabetagamma). Both variants, especially dermokine alphabetagamma-deficient mice exhibited scale and wrinkle formation resembling ichthyosis accompanied by transepidermal water imbalance at the neonatal stage. Several dermokine alphabetagamma-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 alphabetagamma-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 alphabetagamma-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 alphabetagamma-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. |
