The Paracrine Role of Stem Cell Factor/c-kit Signaling in the Activation of Human Melanocytes in Ultraviolet-B-Induced Pigmentation

Abstract

The interaction of stem cell factor with its receptor, c-kit, is well known to be critical to the survival of melanocytes. Little is known about the role(s) of the stem cell factor/c-kit interaction in epidermal pigmentation, however. To clarify whether the stem cell factor/c-kit signaling has a paracrine role in ultraviolet-B-induced pigmentation, we determined whether the exposure of human keratinocytes, melanocytes, and the epidermis to ultraviolet B light stimulates the expression of stem cell factor or c-kit at the gene and/or protein levels. We further examined whether interrupting the binding of stem cell factor to c-kit by subepidermal injection of a monoclonal antibody to c-kit affects ultraviolet-B-induced pigmentation in brownish guinea pig skin. When human keratinocytes and melanocytes in culture were exposed to ultraviolet B light, transcripts of stem cell factor and c-kit (as assessed by reverse transcription polymerase chain reaction) and expression of those proteins (by enzyme-linked immunosorbent assay and western blotting) increased significantly and peaked at a dose of 20-40 mJ per cm2. In ultraviolet-B-exposed human epidermis, stem cell factor transcripts and protein expression were also markedly enhanced compared with the nonexposed epidermis. Immunohistochemistry with antibodies to stem cell factor revealed an increased staining in the ultraviolet-B-exposed epidermis, which was accompanied by a slight epidermal hyperplasia. In the course of ultraviolet-B-induced pigmentation of brownish guinea pig skin, the subepidermal injection of c-kit inhibitory antibodies completely abolished the induction of pigmentation in the ultraviolet-B-exposed area, and there was no increase in the number of dihydroxyphenylalanine-positive melanocytes. These findings indicate that the stem cell factor/c-kit signaling is critically involved in the biologic mechanism of ultraviolet-B-induced pigmentation.

PI3K mediates protection against TRAIL-induced apoptosis in primary human melanocytes

“…47,48 Further, SCF production by keratinocytes is increased by ultraviolet B (UVB) radiation, which is known to increase nevi size and number. 49,50 In the same line, transgenic mice expressing elevated levels of SCF develop melanocyte dysplasia. 51 Thus, SCF by preventing apoptosis in melanocytes could favor melanocyte growth and transformation.…”

The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin

“…1). SCF and bFGF are wellknown melanogenic paracrine factors, especially with respect to responses to UV exposure (Grichnik et al, 1998;Hachiya et al, 2001), but neither of them showed different expression patterns in the various skin types. DKK1 is a paracrine factor responsible for topographical differences of skin color in palm versus trunk skin (Yamaguchi et al, 2004), but although there was quite a variation in expression patterns of DKK1 and the related DKK3, neither of those showed expression patterns that consistently correlated with skin phototype.…”

Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ

“…However of interest, is the relationship of stem cell factor/c-kit to melanocytes, and has been implicated in the proliferation, survival, and migration of embryonic melanoblasts. [20][21] Furthermore, fibroblastic tumor cell-derived stem cell factor may play an important role in melanocyte hyperplasia and hyperpigmentation in dermatofibromas. 13 Utilizing c-kit (CD 117) immunostaining we did note significant staining of dermatofibromas vs the adjacent nonlesional dermis, similar to a previous study.…”