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The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation
Author(s): Hachiya A, Kobayashi A, Ohuchi A, Takema Y, Imokawa G
Source: JOURNAL OF INVESTIGATIVE DERMATOLOGY    Volume: 116    Issue: 4    Pages: 578-586    Published: APR 2001  
Times Cited: 53     References: 51     
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 las 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 cm(2). 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 numb er 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.
Document Type: Article
Language: English
Reprint Address: Imokawa, G (reprint author), Kao Biol Sci Labs, 2606 Akabane, Ichikai, Tochigi 3213497 Japan
Addresses:
1. Kao Biol Sci Labs, Ichikai, Tochigi 3213497 Japan
Publisher: BLACKWELL SCIENCE INC, 350 MAIN ST, MALDEN, MA 02148 USA
Subject Category: Dermatology
IDS Number: 421EA
ISSN: 0022-202X
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