Casein Kinase 1 Inhibition in Keratinocytes Enhances the Migration of Melanocyte Precursors in the Hair Follicle via KitL/c-Kit Signaling Pathway

The study demonstrates that the inhibition of casein kinase 1 (CK1) in keratinocytes can stimulate the migration of melanocyte precursors in the hair follicle, leading to increased eumelanin production in skin and hair shaft. This was established through experiments on Fusion Red-labelled-melanocyte reporter mice, where a topical CK1 inhibitor (CKI) was applied on back skin for 4 weeks. The results showed increased numbers of melanocyte precursor in the secondary hair germ and outer root sheath of hair follicle, and later in the epidermis. The study also found up-regulation of the p53/KitL/c-Kit/MITF/tyrosinase signaling pathway in both types of mice. In human keratinocyte culture, CKI treatment enhanced KitL production and in melanocyte culture, CKI enhanced cell migration. The findings suggest that topical CKI could be a strategy to regenerate melanocyte for conditions like vitiligo or graying hair via activation of the KitL/c-Kit signaling pathway.