title: Sphingolipid-mediated restoration of Mitf expression and repigmentation in vivo in a mouse model of hair graying.
abstract: Recent advances in the identification and characterisation of stem cell populations has led to substantial interest in understanding the precise triggers that would operate to induce activation of quiescent stem cells. Melanocyte stem cells (MSCs) reside in the bulge region of the hair follicles and are characterised by reduced expression of the microphthalmia-associated transcription factor (Mitf) and its target genes implicated in differentiation. Vitiligo is characterised by progressive destruction of differentiated melanocytes. However, therapies using UV irradiation therapy can induce a degree of repigmentation, suggesting that MSCs may be activated. As Mitf is implicated in control of proliferation, we have explored the possibility that inducing Mitf expression via lipid-mediated activation of the p38 stress-signalling pathway may represent a re-pigmentation strategy. Here we have isolated from placental extract a C18:0 sphingolipid able to induce Mitf and tyrosinase expression via activation of the p38 stress-signalling pathway. Strikingly, in age-onset gray-haired C57BL/6J mice that exhibit decaying Mitf expression, topical application of placental sphingolipid leads to increased Mitf in follicular melanocytes and fresh dense black hair growth. The results raise the possibility that lipid-mediated activation of the p38 pathway may represent a novel approach to an effective vitiligo therapy.
authors.affiliation: Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
authors.forename: Bidisha
authors.initials: B
authors.lastname: Saha
authors.forename: Suman Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Shampa
authors.initials: S
authors.lastname: Mallick
authors.forename: Rabindranath
authors.initials: R
authors.lastname: Bera
authors.forename: Pijush K
authors.initials: PK
authors.lastname: Datta
authors.forename: Mriganka
authors.initials: M
authors.lastname: Mandal
authors.forename: Syamal
authors.initials: S
authors.lastname: Roy
authors.forename: Ranjan
authors.initials: R
authors.lastname: Bhadra
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006200:Hair Color; D018859:Hair Follicle / Q000502:physiology; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D023421:Models, Animal; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012880:Skin Pigmentation; D013107:Sphingolipids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D013107:Sphingolipids; D014442:Monophenol Monooxygenase; D020928:Mitogen-Activated Protein Kinases