Characterizing dermokine isoforms in human epidermal equivalents

The epidermis provides a vital barrier between the human body and its external environment, playing critical roles in protection, water retention, and mechanical resistance. Dermokine, a secreted protein produced by suprabasal keratinocytes, is associated with epidermal stratification and terminal differentiation. However, its function has been poorly understood, in part due to its multiple isoforms – dermokine-α, dermokine-β, and dermokine-γ, each with unique domain architectures that contribute to diverse biological processes. In this study, we utilized human skin organoids, which allowed us to monitor epidermal stratification at endogenous dermokine isoform levels using wildtype in comparison to Dmkn αβ-/- and Dmkn βγ-/- keratinocytes. Our results identified that isoform-specific ablation of dermokine led to a disrupted suprabasal stratification detectable both in the histological assessment and various proteomics methods using a human system. By integrating this information, we corroborate that dermokine is involved in the suprabasal epidermal stratification and indirectly influences the abundance of proteins associated with the assembly of the cornified envelope including epidermal proteases.