Colocalization of Cystatin M/E and Its Target Proteases Suggests a Role in Terminal Differentiation of Human Hair Follicle and Nail

The study demonstrated that cystatin M/E, a cysteine protease inhibitor, regulated epidermal terminal differentiation by inhibiting proteases such as cathepsin L, cathepsin V, and legumain. Specifically, cathepsin L was crucial for the cornification process by activating transglutaminase 3, which crosslinks structural proteins in the cornified envelope. The research found that cathepsin L and transglutaminase 3 colocalized in the hair bulb and nail matrix, suggesting their role in the terminal differentiation of hair fibers and nail plates. Additionally, transglutaminase 3 colocalized with loricrin and involucrin, indicating its involvement in the differentiation pathway in both the epidermis and epidermal appendages like hair follicles and nails.