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

    Tsing Cheng, Ivonne M.J.J. van Vlijmen-Willems, Kiyotaka Hitomi, Marcel C. Pasch, P.E.J. van Erp, Joost Schalkwijk, Patrick L.J.M. Zeeuwen
    TLDR Cystatin M/E helps in the final stages of hair and nail formation by controlling certain enzymes.
    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.
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