Identification of serpin B12 as an endogenous inhibitor of epidermal mesotrypsin and its possible role in epidermal desquamation during differentiation.

The maintenance of stratum corneum homeostasis requires precise regulation of protease activity, particularly within the desquamation pathway. In this study, we identified serpin B12 as an inhibitor of mesotrypsin in stratum corneum extracts obtained from hyperkeratotic heel skin. liquid chromatography coupled with electrospray ionization tandem mass spectrometry analysis identified serpin B12 as one of the most abundant candidates with known mesotrypsin-inhibitory potential, and recombinant serpin B12 suppressed mesotrypsin activity in a dose-dependent manner. To evaluate its functional relevance in epidermal tissue, we manipulated serpin B12 expression in reconstructed 3-dimensional skin equivalents. Knockdown and overexpression of serpin B12 resulted in marked alterations in stratum corneum thickness, indicating that serpin B12 influences the structural organization of the upper epidermis. Because mesotrypsin modulates kallikrein-related peptidases, which mediate corneodesmosome degradation and desquamation, these findings suggest that serpin B12 contributes to the modulation of stratum corneum homeostasis through the inhibition of mesotrypsin activity. Our results suggest that serpin B12 functions as an epidermal protease inhibitor and provide insight into the molecular mechanisms governing barrier maintenance.

Abstract from PubMed