Serpinb7, a serine protease inhibitor, is crucial for maintaining normal physiological functions. It is known to play a role in regulating proteases, which are involved in various signaling cascades in the body. Genetic models, such as knockout (KO) mouse models, have been instrumental in understanding its functions [1,2].

In skin-related research, Serpinb7-deficient mice showed abnormal epidermal barrier integrity and skin architecture at homeostasis. In a psoriasis model induced by imiquimod, Serpinb7 -/- mice had aggravated psoriatic lesions with inhibited terminal differentiation and increased inflammatory cell infiltration compared to Serpinb7+/+ mice. Mechanistically, Serpinb7 deficiency led to excessive keratinocyte proliferation, impaired differentiation, and increased chemokine and antimicrobial peptide expression, possibly by affecting calcium-ion-channel-related proteins and intracellular Ca2+ influx [1]. In Nagashima-type palmoplantar keratoderma, Serpinb7 -/- mice spontaneously developed a disrupted skin barrier, with weakened cytoskeletal proteins and decreased epidermal differentiation. SERPINB7 was found to inhibit the protease legumain, and its deficiency led to over-activation of legumain, contributing to the impaired skin barrier [2].

In conclusion, Serpinb7 plays essential roles in maintaining skin integrity, especially in keratinocyte differentiation and epidermal barrier function. The use of Serpinb7 KO mouse models has significantly enhanced our understanding of its role in psoriasis and Nagashima-type palmoplantar keratoderma, potentially paving the way for new therapeutic strategies in these skin diseases [1,2].

References:

1. Zheng, Huaping, Gu, Linna, Zhao, Fulei, Li, Wei, Li, Jiong. 2022. SerpinB7 deficiency contributes to development of psoriasis via calcium-mediated keratinocyte differentiation dysfunction. In Cell death & disease, 13, 635. doi:10.1038/s41419-022-05045-8. https://pubmed.ncbi.nlm.nih.gov/35864103/

2. Li, Siyuan, Wu, Yingda, Bu, Dingfang, Gu, Heng, Yang, Yong. 2024. SERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-Type Palmoplantar Keratoderma. In The Journal of investigative dermatology, 145, 359-369.e8. doi:10.1016/j.jid.2024.05.025. https://pubmed.ncbi.nlm.nih.gov/38909841/