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FK 506 regulates pigmentation by maturing the melanosome and facilitating their transfer to keratinocytes
Author(s) -
Jung Hyejung,
Chung Heesung,
Chang Sung Eun,
Kang DukHee,
Oh EokSoo
Publication year - 2016
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/pcmr.12443
Subject(s) - melanosome , tyrosinase , melanin , hacat , microbiology and biotechnology , vitiligo , keratinocyte , melanocyte , secretion , biology , chemistry , melanoma , cell culture , cancer research , enzyme , biochemistry , immunology , genetics
Summary Despite the clinical ability of topical tacrolimus ( FK 506) to effectively promote repigmentation in vitiligo, the underlying mechanism through which FK 506 regulates melanogenesis was previously unclear. We found that FK 506 treatment increased the melanin contents (especially that of eumelanin) in both melanocytes and melanoma cells. This treatment did not affect the transcription levels of tyrosinase, suggesting that FK 506 increases melanin synthesis by regulating cellular levels of tyrosinase. Interestingly, FK 506 promoted melanosome maturation by increasing melanosomal pH (a marker of melanosome maturation), thereby enhancing the stability of melanosome‐localized tyrosinase. In addition, FK 506 enhanced UVB ‐mediated melanosome secretion, the uptake of melanosomes by HaCaT cells, and the transfer of melanosomes to keratinocytes co‐cultured with melanocytes. Together, these findings suggest that FK 506 contributes to melanin synthesis by regulating the maturation of melanosomes and their transfer to keratinocytes. This offers a novel regulatory mechanism through which FK 506 and UVB can have a combined effect on melanogenesis.