Role of Cell Death in Differentiation of Skin Keratinocytes

This review examines the role of regulated cell death (RCD) in differentiation and maintenance of the barrier properties of the skin epidermis under normal and pathological conditions. The differentiation process involves activation of the mechanisms such as endoplasmic reticulum (ER) stress, macroautophagy, and corneoptosis. Responses to abiotic stresses include apoptosis, pyroptosis, necroptosis, and mitotic catastrophe. Polyploidization of keratinocytes and their transition to a senescent state could be considered as adaptive responses that preserve barrier properties of the epidermis. The balance between various forms of cell death and adaptive mechanisms - such as polyploidization and senescence is a key factor in establishing and maintaining the skin barrier function. Disruptions in this balance underlie many dermatoses and age-related changes. Understanding molecular mechanisms of these processes opens avenues for the development of the targeted therapies aimed at restoring barrier properties of the epidermis.