Wnt/β-Catenin and Kit Signaling Sequentially Regulate Melanocyte Stem Cell Differentiation in UVB-Induced Epidermal Pigmentation

Abstract

UV radiation is a well-known inducer of epidermal pigmentation that is utilized in therapy for vitiligo, one of the skin depigmentation disorders. Although it has been reported that melanocyte stem cells (McSCs) play essential roles in hair pigmentation, the relationship between McSCs and epidermal pigmentation remains unclear. Repetitive UVB irradiation on the dorsal skin of F1 mice of HR-1 × HR/De caused apparent epidermal pigmentation, and it was characterized by increase in the number of melanocytes. Interestingly, differentiation of McSCs into melanoblasts in hair follicles was followed by induction of epidermal melanocyte differentiation. Administration of a neutralizing antibody for Kit receptor that depletes resident melanoblasts could not suppress increased number of melanocytes. UVB irradiation also induced robust expression of Wnt7a as well as Kitl in epidermis, and β-catenin translocation into nucleus in McSCs. Intradermal injection of IWR-1 (inhibitor of Wnt response 1), a chemical inhibitor of β-catenin activation, and small interfering RNA (siRNA) against Wnt7a suppressed increase in the number of epidermal melanocytes. Taken altogether, it was demonstrated that Wnt7a triggered McSCs differentiation through β-catenin activation, and Kitl might induce following migration of melanoblasts to epidermis. These findings will help in developing therapeutic technologies for vitiligo and other pigmentary disorders.

siRNA-based spherical nucleic acids reverse impaired wound healing in diabetic mice by ganglioside GM3 synthase knockdown

“…SNA constructs are able to penetrate the stratum corneum of intact skin, rapidly enter epidermal and dermal cells, and knock down epidermal targets (17). In contrast to SNAs, other topical siRNAbased therapies require epidermal disruption by physical [e.g., injection, tape stripping (23), laser, or ultrasound] or chemical (e.g., conjugation to peptides or lipoplexes or incorporation into other types of nanoparticle structures, lentiviruses, or gels) means for RNAi penetration through the epidermal barrier and into KCs (24)(25)(26)(27)(28)(29)(30)(31). siRNA SNAs are unique, highly anionic constructs that do not require additional chemical modifications to facilitate transportation through the stratum corneum or entry into cells.…”

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

“…Moreover, a separate study reported that epidermal keratinocytes and epidermal melanocytes secrete Wnt7 upon UVB exposure. Secreted Wnt7 was then responsible for melanocyte stem cell differentiation through the activation of Wnt/β-catenin signaling pathway [26]. Additionally, we have found that mROS were transiently increased upon 60 sec of laser treatment.…”

Paracrine Secreted Frizzled-Related Protein 4 Inhibits Melanocytes Differentiation in Hair Follicle

“…Third and most important, it is also reasonable to speculate that the skin evolves multiple ways to protect organism from environmental insult [47]. For example, the UV radiation induces melanocytes differentiation to prevent the skin from injury [53]. Thus, under normal conditions, the neighboring epithelia-secreted factors further serve to enhance the quiescent state of melanocytes to prevent them from overdifferentiation.…”