Dual Regulation of Corneodesmosome Formation by Shotokuseki Extract Enhances Skin Barrier Homeostasis

Corneodesmosomes are specialized intercellular junctions that mediate adhesion between corneocytes in the stratum corneum (SC). The degradation of these structures is regulated by kallikrein-related peptidases (KLKs) and their inhibitors. This study aimed to elucidate the effects of Shotokuseki extract (SE), a substance rich in various trace elements, on molecules related to SC adhesion using a three-dimensional cultured human epidermis model. SE was applied to a three-dimensional epidermis model, and analyses were conducted on gene expression, protease activity, protein levels, and tissue structure. SE treatment significantly upregulated the mRNA expression of corneodesmosomal components (desmoglein1, desmocollin1, and corneodesmosin) and the major protease inhibitor serine peptidase inhibitor Kazal type 5. Concurrently, SE increased the mRNA expression of the trypsin-like protease KLK5,while significantly decreasing the mRNA expression and activity of the chymotrypsin-like protease KLK7. Although no significant changes were observed in the protein levels of corneodesmosomal components, histological analysis revealed that SE significantly increased the ratio of SC thickness to total epidermal thickness. These findings suggest that SE contributes to the homeostasis of the SC by simultaneously promoting the expression of genes encoding corneodesmosomal components, and regulating the balance of the protease/inhibitor system involved in their degradation. The selective suppression of KLK7 activity may appropriately regulate the final stage of desquamation, thereby stabilizing barrier function.