Downregulated melanogenic paracrine cytokine linkages in hypopigmented palmoplantar skin.
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, S100alpha, c-KIT, endothelin B receptor (ETBR), 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.
Hasegawa
Junichi
J
Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan 2 School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
Goto
Yasufumi
Y
Murata
Hiroshi
H
Takata
Minoru
M
Saida
Toshiaki
T
Imokawa
Genji
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D015536:Down-Regulation; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005528:Foot; D005786:Gene Expression Regulation; D006225:Hand; D006801:Humans; D017496:Hypopigmentation / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D008544:Melanocytes / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D019899:Paracrine Communication; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012880:Skin Pigmentation; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; D019332:Endothelin-1; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D012333:RNA, Messenger; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D019089:Stem Cell Factor; D004295:Dihydroxyphenylalanine; D019009:Proto-Oncogene Proteins c-kit