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Downregulated melanogenic paracrine cytokine linkages in hypopigmented palmoplantar skin
Author(s) -
Hasegawa Junichi,
Goto Yasufumi,
Murata Hiroshi,
Takata Minoru,
Saida Toshiaki,
Imokawa Genji
Publication year - 2008
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.2008.00492.x
Subject(s) - microphthalmia associated transcription factor , melanocyte , paracrine signalling , biology , immunohistochemistry , tyrosinase , epidermis (zoology) , stem cell factor , wnt signaling pathway , keratinocyte , microbiology and biotechnology , endocrinology , receptor , medicine , cancer research , signal transduction , immunology , cell culture , stem cell , anatomy , melanoma , haematopoiesis , enzyme , biochemistry , genetics
Summary The hypo‐pigmentation of human skin on the palms and the soles compared with other areas of the body has recently been reported to be due to mesenchymal–epithelial interactions via a fibroblast‐derived factor, dickkopf 1, an inhibitor of the canonical Wnt signaling pathway. Recently, it has been reported that keratinocytes play a significant role in skin color determination by producing cytokines involved in melanogenesis. Thus, we hypothesized that the downregulated expression of keratinocyte‐ or fibroblast‐derived melanogenic cytokines may also be responsible for the decreased function of palmoplantar (PP) melanocytes in addition to the suppressive effects of dickkopf 1 on melanogenic function in epidermal melanocytes. Immunohistochemistry revealed that the number of tyrosinase, S100α, c‐KIT, endothelin B receptor (ET B R), SOX10, and microphthalmia‐associated transcription factor (MITF) immuno‐positive melanocytes is significantly reduced in PP epidermis. In contrast, dopa‐histochemistry demonstrated no substantial reduction in melanocyte populations in PP epidermis. Real‐time RT‐PCR revealed that the expression of stem cell factor (SCF) and endothelin (ET)‐1 mRNAs in PP skin was significantly downregulated. In parallel, immunohistochemistry revealed that SCF and ET‐1 immuno‐staining was markedly attenuated in PP skin. Western blotting revealed that the expression of SCF, c‐KIT, and MITF‐M proteins was significantly decreased in PP skin. These findings suggest the possibility that downregulation of ET‐1/SCF/receptor linkages is also associated with the decreased function of melanocytes in PP skin.