UV-Induced Keratin 1 Proteolysis Mediates UV-Induced Skin Damage

Keratins play critical roles in intermediate filament formation, inflammatory responses and cellular signaling in epithelium. While keratins is a major epidermal fluorophore, the mechanisms underlying the autofluorescence (AF) of keratins and its biomedical implications have remained unknown. Our study used mouse skin as a model to study these topics, showing that UV dose-dependently induced increases in green AF at the spinous layer of the epidermis of mouse within 6 hr of the UV exposures, which may be used for non-invasive prediction of UV-induced skin damage. The UV-induced AF appears to be induced by cysteine protease-mediated keratin 1 proteolysis: 1) UV rapidly induced significant keratin 1 degradation; 2) administration of keratin 1 siRNA largely decreased the UV-induced AF; and 3) administration of E-64, a cysteine protease inhibitor, significantly attenuated the UV-induced AF and keratin 1 degradation. Our study has also suggested that the UV-induced keratin 1 proteolysis may be a novel crucial pathological factor in UV-induced skin damage, which is supported by both the findings that indicate critical biological roles of keratin 1 in epithelium and our observation that prevention of UV-induced keratin 1 proteolysis can lead to decreased UV-induced skin damage. Collectively, our study has suggested that UV-induced keratin 1 proteolysis may be a novel and valuable target for diagnosis, prevention and treatment of UV-induced skin damage.