title: Protective effect of Kit signaling for melanocyte stem cells against radiation-induced genotoxic stress.
abstract: Radiation-induced hair graying is caused by irreversible defects in the self-renewal and/or development of follicular melanocyte stem cells in the hair follicles. Kit signaling is an essential growth and differentiation signaling pathway for various cell lineages including melanocytes, and its radioprotective effects have been shown in hematopoietic cells. However, it is uncertain whether Kit signaling exerts a radioprotective effect for melanocytes. In this study, we found that various loss-of-function mutations of Kit facilitate radiation-induced hair graying. In contrast, transgenic mice expressing the ligand for Kit (Kitl) in the epidermis have significantly reduced levels of radiation-induced hair graying. The X-ray doses used did not show a systemic lethal effect, indicating that the in vivo radiosensitivity of Kit mutants is mainly caused by the damaged melanocyte stem cell population. X-ray-damaged melanocyte stem cells seemed to take the fate of ectopically pigmented melanocytes in the bulge regions of hair follicles in vivo. Endothelin 3, another growth and differentiation factor for melanocytes, showed a lesser radioprotective effect compared with Kitl. These results indicate the prevention of radiation-induced hair graying by Kit signaling.
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Aoki
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Motohashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D019070:Cell Lineage / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D019610:Cytoprotection / Q000502:physiology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006200:Hair Color / Q000502:physiology* / Q000528:radiation effects*; D018859:Hair Follicle / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D007763:Lac Operon / Q000235:genetics; D008544:Melanocytes / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D013312:Stress, Physiological / Q000502:physiology* / Q000528:radiation effects*
chemical_list: D019009:Proto-Oncogene Proteins c-kit