title: FK506 regulates pigmentation by maturing the melanosome and facilitating their transfer to keratinocytes.
abstract: Despite the clinical ability of topical tacrolimus (FK506) to effectively promote repigmentation in vitiligo, the underlying mechanism through which FK506 regulates melanogenesis was previously unclear. We found that FK506 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 FK506 increases melanin synthesis by regulating cellular levels of tyrosinase. Interestingly, FK506 promoted melanosome maturation by increasing melanosomal pH (a marker of melanosome maturation), thereby enhancing the stability of melanosome-localized tyrosinase. In addition, FK506 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 FK506 contributes to melanin synthesis by regulating the maturation of melanosomes and their transfer to keratinocytes. This offers a novel regulatory mechanism through which FK506 and UVB can have a combined effect on melanogenesis.
authors.affiliation: Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Korea.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Korea.
authors.forename: Heesung
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Ewha Medical Research Center, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.affiliation: Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Korea.
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000648:ultrastructure; D008543:Melanins / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects; D016559:Tacrolimus / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D016559:Tacrolimus
keywords: FK506; melano-some; melanogenesis; tyrosinase; vitiligo