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Sphingolipid‐mediated restoration of Mitf expression and repigmentation in vivo in a mouse model of hair graying
Author(s) -
Saha Bidisha,
Singh Suman Kumar,
Mallick Shampa,
Bera Rabindranath,
Datta Pijush K.,
Mandal Mriganka,
Roy Syamal,
Bhadra Ranjan
Publication year - 2009
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00548.x
Subject(s) - microphthalmia associated transcription factor , microbiology and biotechnology , biology , hair follicle , sphingolipid , stem cell , transcription factor , hair cycle , melanocyte , sox10 , hedgehog signaling pathway , signal transduction , cancer research , melanoma , neural crest , genetics , gene , embryo
Summary 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.