Cited by 369melanin and skin pigmentationMelanoma and MAPK PathwaysDermatologic Treatments and Research

Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders

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Imokawa, Genji·2004·Pigment Cell Research

Abstract

Recently melanogenic paracrine or autocrine cytokine networks have been discovered in vitro between melanocytes and other types of skin cells. These include endothelin (ET)‐1, granulocyte macrophage colony stimulating factor, membrane‐type stem cell factor (SCF) and growth‐related oncogene‐α for interactions between keratinocytes and melanocytes, and hepatocyte growth factor and soluble type SCF for interactions between fibroblasts and melanocytes. These networks are also associated with corresponding receptors expressed on melanocytes, including ET B receptor and the SCF receptor, c‐KIT. Consistent with in vitro findings on the melanogenic paracrine or autocrine cytokine networks, we have found that the up‐ or down‐regulation of such networks is intrinsically involved in vivo in the stimulation of melanocyte functions in several epidermal hyper‐ or hypo‐pigmentary disorders. These are ET‐1/ET B receptor as well as membrane type SCF/c‐KIT for ultraviolet B‐melanosis, granulocyte macrophage colony stimulating factor for ultraviolet A‐melanosis, ET‐1/ET B receptor as well as membrane type SCF for lentigo senilis, growth related oncogene‐α for Riehl's melanosis, sphingosylphosphorylcholine for hyperpigmentation in atopic dermatitis, ET‐1 for seborrhoeic keratosis, soluble type SCF as well as hepatocyte growth factor for dermatofibroma and café‐au‐lait macules, and c‐KIT for vitiligo vulgaris. These unveiled regulatory mechanisms involved in the abnormal up‐ or down‐regulated levels of lesional melanocyte function provide new insights into therapeutic tools utilizing blockage of responsible cytokine networks.

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Research works printed but not linked: 8

  1. Imokawa G, Yada Y, Kimura M. Signaling mechanisms of endo- thelin-induced mitogenesis in human melanocytes. Biochem J 1996;314:305-312
  2. Chakraborty AK, Funasaka Y, Slominski A, Ermak G, Hwang J, Pawelek J, Ichihashi M. Production and release of proopiomelano- cortin (POMC) derived peptides by human melanocytes and kera- tinocytes in culture: regulation by UVB. Biochim Biophys Acta 1996;1313:130-138
  3. Imokawa G, Yada Y, Morisaki N, Kimura M. Characterization of keratinocyte-and fibroblast-derived mitogens for human melanocyte -their roles in stimulated cutaneous pigmentation. In: Hori Y, Hearing VJ, Nakayama J, ed. Melanogenesis and Malignant Mel- anoma. London: Elsevier Science B.V.; 1996. pp. 35-48
  4. Higuchi K, Kawashima M, Ichikawa Y, Imokawa G. Sphingosyl- phosphorylcholine is a melanogenic stimulator for human melano- cytes. Pigment Cell Res 2003;16:670-678
  5. Colver GB, Mortimer PS, Millard PR, Dawber RPR, Ryan TJ. The ÔDirty NeckÕ -a reticulate pigmentation in atopics. Clin Exp Dermatol 1987;12:1-4
  6. Longley BJ, Morganroth GS, Tyrrell L, Ding TG, Anderson DM, Williams DE, Halaban R. Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis. N Engl J Med 1993;328:1302-1307
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Authors
Imokawa, G.
Corresponding author
Imokawa, Genji
Venue
Pigment Cell Research
Publisher
Wiley
Published
2004-03-11
Volume
17
Issue
2
Pages
96-110
ISSN
  • 0893-5785 (ISSN-L)
  • 1600-0749
OpenAlex
W2138112259
Cited by
369
References
105
Citations by year
2026: 7 · 2025: 3 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 7 · 2020: 18 · 2019: 18 · 2018: 20 · 2017: 15 · 2016: 17 · 2015: 17 · 2014: 19 · 2013: 21 · 2012: 19
FWCI
1.47
Type
journal article
Language
en
Open access
Locations
  • Pigment Cell Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
Keywords
melanocytes, autocrine regulation, paracrine regulation, cytokine network, endothelin-1, endothelin B receptor, stem cell factor, CD117, GM-CSF, hepatocyte growth factor, growth-related oncogene alpha, keratinocytes, fibroblasts, Riehl's melanosis, seborrheic keratosis, dermatofibroma, café-au-lait spots, vitiligo, skin pigmentation disorders, melanocyte function
MeSH terms
Fibroblasts, Humans, Melanocytes, Models, Biological, Pigmentation, Skin, Ultraviolet Rays, Down-Regulation, Keratinocytes, Up-Regulation, Proto-Oncogene Proteins c-kit, Stem Cell Factor

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